lignans and Neoplasms

lignans has been researched along with Neoplasms* in 111 studies

Reviews

53 review(s) available for lignans and Neoplasms

ArticleYear
Podophyllotoxin and its derivatives: Potential anticancer agents of natural origin in cancer chemotherapy.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2023, Volume: 158

    The use of plant secondary metabolites has gained considerable attention among clinicians in the prevention and treatment of cancer. A secondary metabolite isolated mainly from the roots and rhizomes of Podophyllum species (Berberidaceae) is aryltetralin lignan - podophyllotoxin (PTOX). The purpose of this review is to discuss the therapeutic properties of PTOX as an important anticancer compound of natural origin. The relevant information regarding the antitumor mechanisms of podophyllotoxin and its derivatives were collected and analyzed from scientific databases. The results of the analysis showed PTOX exhibits potent cytotoxic activity; however, it cannot be used in its pure form due to its toxicity and generation of many side effects. Therefore, it practically remains clinically unusable. Currently, high effort is focused on attempts to synthesize analogs of PTOX that have better properties for therapeutic use e.g. etoposide (VP-16), teniposide, etopophos. PTOX derivatives are used as anticancer drugs which are showing additional immunosuppressive, antiviral, antioxidant, hypolipemic, and anti-inflammatory effects. In this review, attention is paid to the high potential of the usefulness of in vitro cultures of P. peltatum which can be a valuable source of lignans, including PTOX. In conclusion, the preclinical pharmacological studies in vitro and in vivo confirm the anticancer and chemotherapeutic potential of PTOX and its derivatives. In the future, clinical studies on human subjects are needed to certify the antitumor effects and the anticancer mechanisms to be certified and analyzed in more detail and to validate the experimental pharmacological preclinical studies.

    Topics: Antineoplastic Agents; Antiviral Agents; Humans; Lignans; Neoplasms; Podophyllotoxin

2023
The therapeutic potential of arctigenin against multiple human diseases: A mechanistic review.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2023, Volume: 110

    Arctigenin (ATG), a dibenzyl butyrolactone lignan compound, is one of the major bioactive components from the medicinal plant Arctium lappa. ATG possesses remarkable therapeutic potential against a wide range of human diseases, such as cancers, immune disorders and chronical diseases. The molecular mechanisms behind the biological effects of ATG have been intensively studied.. This review aims to systematically summarize the updated knowledge of the proteins and signaling pathways behind the curative property of ATG, and further analyze the potential connections between them.. SciFinder, Pubmed, Web of Science and Cochrane Library databases were queried for publications reporting the therapeutic properties of ATG. "Arctigenin", "disease", "cancer", "inflammation", "organ damage", "infection", "toxicity" and "pharmacokinetics" were used as the searching titles.. 625 publications were identified and 95 met the inclusion criteria and exclusion criteria. 42 studies described the molecular mechanisms implicated in ATG treatments. Several proteins including phosphodiesterase subtype 4D (PDE4D), estrogen receptor (ER) β, protein phosphatase 2A (PP2A), phosphoinositide 3-kinase (PI3K) and transmembrane protein 16A (TMEM16A) are targeted by ATG in different settings. The frequently described signaling pathways are TLR4/NF-κB, PI3K/AKT/mTOR, AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf-2) signalings.. Inhibition of PI3K/AKT pathway and activation of AMPK signaling play the pivotal roles in the therapeutic effects of ATG. PI3K/AKT and AMPK signaling widely link to other signaling pathways, modulating various biological processes such as anti-inflammation, anti-oxidative stress, anti-fibrosis, anti-ER stress, anti-steatosis and pro-apoptosis, which constitute the curative mechanisms of ATG against multiple human diseases.

    Topics: AMP-Activated Protein Kinases; Furans; Humans; Lignans; Neoplasms; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt

2023
Anticancer Potentials of the Lignan Magnolin: A Systematic Review.
    Molecules (Basel, Switzerland), 2023, Apr-23, Volume: 28, Issue:9

    Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer properties of magnolin. For this, a recent (as of March 2023) literature review was conducted using various academic search engines, including PubMed, Springer Link, Wiley Online, Web of Science, Science Direct, and Google Scholar. All the currently available information about this phytochemical and its role in various cancer types has been gathered and investigated. Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways. In conclusion, magnolin showed robust anticancer activity against many cancer cell lines by altering several cancer signaling pathways in various non- and pre-clinical experimental models, making it a promising plant-derived chemotherapeutic option for further clinical research.

    Topics: Cell Cycle; Humans; Lignans; Neoplasms; Phytochemicals; Signal Transduction

2023
Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship.
    Chemico-biological interactions, 2023, Dec-01, Volume: 386

    Lignans are plant-derived polyphenolic compounds with a plethora of biological applications. Also, regarded as phytoestrogens, the lignans offer a variety of health benefits of which the anti-cancer effects are the most attractive. Honokiol is a lignan isolated from various parts of trees belonging to the genus Magnolia. The bioactivity of honokiol is attributed to its characteristic physical properties, which include small size and the presence of two phenolic groups that may interact with proteins in cell membranes via hydrophobic interactions, aromatic pi orbital co-valency, and hydrogen bonding. The hydrophobicity of honokiol enables its rapid dissolution in lipids and the crossing of physiological barriers, including the blood-brain barrier and cerebrospinal fluid. These factors contribute towards the high bioavailability of honokiol which further support its candidature in medicinal research. Therefore, the anticancer properties of honokiol are of particular interest as many of the contemporary anticancer drugs suffer from bioavailability drawbacks, which necessitates the identification and development of novel candidate molecules directed as anticancer chemotherapeutics. The antioncogenic profile of honokiol also arises from the regulation of various signalling pathways associated with oncogenesis, arresting of the cell cycle by regulation of cyclic proteins, upregulation of epithelial markers and downregulation of mesenchymal markers leading to the inhibition of epithelial-mesenchymal transition, and preventing the metastasis by restricting cell migration and invasion due to the downregulation of matrix-metalloproteinases. In this review, we discuss the anticancer properties of honokiol.

    Topics: Biphenyl Compounds; Cell Line, Tumor; Humans; Lignans; Neoplasms; Phenols; Structure-Activity Relationship

2023
Exploiting the tumor immune microenvironment and immunometabolism using mitochondria-targeted drugs: Challenges and opportunities in racial disparity and cancer outcome research.
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022, Volume: 36, Issue:4

    Black and Hispanic cancer patients have a higher incidence of cancer mortality. Many factors (e.g., socioeconomic differences, insufficient access to healthcare) contribute to racial disparity. Emerging research implicates biological disparity in cancer outcomes. Studies show distinct differences in the tumor immune microenvironment (TIME) in Black cancer patients. Studies also have linked altered mitochondrial metabolism to changes in immune cell activation in TIME. Recent publications revealed a novel immunomodulatory role for triphenylphosphonium-based mitochondrial-targeted drugs (MTDs). These are synthetically modified, naturally occurring molecules (e.g., honokiol, magnolol, metformin) or FDA-approved small molecule drugs (e.g., atovaquone, hydroxyurea). Modifications involve conjugating the parent molecule via an alkyl linker chain to a triphenylphosphonium moiety. These modified molecules (e.g., Mito-honokiol, Mito-magnolol, Mito-metformin, Mito-atovaquone, Mito-hydroxyurea) accumulate in tumor cell mitochondria more effectively than in normal cells and inhibit mitochondrial respiration, induce reactive oxygen species, activate AMPK and redox transcription factors, and inhibit cancer cell proliferation. Besides these intrinsic effects of MTDs in redox signaling and proliferation in tumors, MTDs induced extrinsic effects in the TIME of mouse xenografts. MTD treatment inhibited tumor-suppressive immune cells, myeloid-derived suppressor cells, and regulatory T cells, and activated T cells and antitumor immune effects. One key biological disparity in Black cancer patients was related to altered mitochondrial oxidative metabolism; MTDs targeting vulnerabilities in tumor cells and the TIME may help us understand this biological disparity. Clinical trials should include an appropriate number of Black and Hispanic cancer patients and should validate the intratumoral, antihypoxic effects of MTDs with imaging.

    Topics: Atovaquone; Biphenyl Compounds; Black People; Health Status Disparities; Hispanic or Latino; Humans; Immune Checkpoint Inhibitors; Lignans; Mitochondria; Neoplasms; Oxidative Phosphorylation; Tumor Microenvironment

2022
Therapeutic Potential of Naturally Occurring Lignans as Anticancer Agents.
    Current topics in medicinal chemistry, 2022, Volume: 22, Issue:17

    Cancer is a long-term and deadly pandemic that affects nearly a third of the world's population. Chemotherapy is currently the most common therapeutic treatment, but it is difficult to achieve satisfactory efficacy due to drug resistance and adverse effects.Natural products are becoming increasingly popular in cancer therapy due to their potent broad-spectrum anticancer potency and slight side effects. Lignans are complex diphenolic compounds comprising a family of secondary metabolites existing widely in plants. Naturally occurring lignans have the potential to act on cancer cells by a range of mechanisms of action and could inhibit the colony formation, arrest the cell cycle in different phases, induce apoptosis, and suppress migration, providing privileged scaffolds for the discovery of novel anticancer agents. In recent five years, a variety of naturally occurring lignans have been isolated and screened for their in vitro and/or in vivo anticancer efficacy, and some of them exhibited promising potential. This review has systematically summarized the resources, anticancer activity, and mechanisms of action of naturally occurring lignans, covering articles published between January 2017 and January 2022.

    Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Humans; Lignans; Neoplasms

2022
A comprehensive insight into the antineoplastic activities and molecular mechanisms of deoxypodophyllotoxin: Recent trends, challenges, and future outlook.
    European journal of pharmacology, 2022, Aug-05, Volume: 928

    Lignans constitute an important group of polyphenols, which have been demonstrated to potently suppress cancer cell proliferation. Numerous in vitro and in vivo studies indicate that deoxypodophyllotoxin as a natural lignan possesses potent anticancer activities against various types of human cancer. The purpose of current review is to provide the reader with the latest findings in understanding the anticancer effects and molecular mechanisms of deoxypodophyllotoxin. This review comprehensively describes the influence of deoxypodophyllotoxin on signaling cascades and molecular targets implicated in cancer cell proliferation and invasion. A number of various signaling molecules and pathways, including apoptosis, necroptosis, cell cycle, angiogenesis, vascular disruption, ROS, MMPs, glycolysis, and microtubules as well as NF-κB, PI3K/Akt/mTOR, and MAPK cascades have been reported to be responsible for the anticancer activities of deoxypodophyllotoxin. The results of present review suggest that the cyclolignan deoxypodophyllotoxin can be developed as a novel and potent anticancer agent, especially as an alternative option for treatment of resistant tumors to chemotherapy.

    Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Drugs, Chinese Herbal; Humans; Lignans; Neoplasms; Phosphatidylinositol 3-Kinases; Podophyllotoxin

2022
Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites.
    International journal of molecular sciences, 2022, Dec-07, Volume: 23, Issue:24

    Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.

    Topics: Anti-Inflammatory Agents; Antioxidants; Cardiovascular Diseases; Humans; Lignans; Neoplasms; NF-kappa B; Phytoestrogens

2022
A comprehensive mechanistic insight into the dietary and estrogenic lignans, arctigenin and sesamin as potential anticarcinogenic and anticancer agents. Current status, challenges, and future perspectives.
    Critical reviews in food science and nutrition, 2022, Volume: 62, Issue:26

    A large body of evidence indicates that lignans as polyphenolic compounds are beneficial against life-threatening diseases such as cancer. Plant lignans have the potential to induce cancer cell death and interfere with carcinogenesis, tumor growth, and metastasis. Epidemiological studies have revealed that the intake of lignans is inversely associated with the risk of several cancers. Moreover, numerous experimental studies demonstrate that natural lignans significantly suppress cancer cell proliferation with minimal toxicity against non-transformed cells. Dietary lignans arctigenin and sesamin have been found to have potent antiproliferative activities against various types of human cancer. The purpose of this review is to provide the reader with a deeper understanding of the cellular and molecular mechanisms underlying anticancer effects of arctigenin and sesamin. Our review comprehensively describes the effects of arctigenin and sesamin on the signaling pathways and related molecules involved in cancer cell proliferation and invasion. The findings of present review show that the dietary lignans arctigenin and sesamin seem to be promising carcinopreventive and anticancer agents. These natural lignans can be used as dietary supplements and pharmaceuticals for prevention and treatment of cancer.

    Topics: Antineoplastic Agents; Cell Line, Tumor; Dioxoles; Furans; Humans; Lignans; Neoplasms

2022
Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss".
    Cellular and molecular biology (Noisy-le-Grand, France), 2021, Sep-29, Volume: 67, Issue:2

    There has been an exponential growth in the field of molecular oncology and cutting-edge research has enabled us to develop a better understanding of therapeutically challenging nature of cancer. Based on the mechanistic insights garnered from decades of research, puzzling mysteries of multifaceted nature of cancer have been solved to a greater extent. Our rapidly evolving knowledge about deregulated oncogenic cell signaling pathways has allowed us to dissect different oncogenic transduction cascades which play critical role in cancer onset, progression and metastasis. Pharmacological targeting of deregulated pathways has attracted greater than ever attention in the recent years. Henceforth, discovery and identification of high-quality biologically active chemicals and products is gaining considerable momentum. There has been an explosion in the dimension of natural product research because of tremendous potential of chemopreventive and pharmaceutical significance of natural products. Schisandrin is mainly obtained from Schisandra chinensis. Schisandrin has been shown to be effective against different cancers because of its ability to inhibit/prevent cancer via modulation of different cell signaling pathways. Importantly, regulation of non-coding RNAs by schisandrin is an exciting area of research that still needs detailed and comprehensive research.   However, we still have unresolved questions about pharmacological properties of schisandrin mainly in context of its regulatory role in TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways.

    Topics: Animals; Apoptosis; Carcinogenesis; Cell Movement; Clinical Trials as Topic; Cyclooctanes; Gene Expression Regulation, Neoplastic; Humans; Lignans; Neoplasms; Plant Extracts; Polycyclic Compounds; Protein Interaction Maps; Schisandra; Signal Transduction; Treatment Outcome

2021
Dietary phytoestrogens and biomarkers of their intake in relation to cancer survival and recurrence: a comprehensive systematic review with meta-analysis.
    Nutrition reviews, 2021, 01-01, Volume: 79, Issue:1

    Recent studies have outlined the potential role of dietary factors in patients who have survived cancer.. The aim of this study was to summarize the evidence of the relation between dietary intake of phytoestrogens and their blood biomarkers and, overall, cancer-specific mortality and recurrence in patients with cancer.. A systematic search of PubMed, EMBASE, and Web of Science databases of studies published up to September 2019 was performed. Databases were searched for prospective and retrospective cohort studies reporting on dietary phytoestrogen intake and/or blood biomarkers and the outcomes investigated.. Data were extracted from each identified study using a standardized form.. Twenty-eight articles on breast, lung, prostate, and colorectal cancer, and glioma were included for systematic review. Given the availability of studies, a quantitative meta-analysis was performed solely for breast cancer outcomes. A significant inverse association among higher dietary isoflavone intake, higher serum/plasma enterolactone concentrations, and overall mortality and cancer recurrence was found. Among other cancer types, 2 studies reported that higher serum enterolactone and higher intake of lignans were associated with cancer-specific survival for colorectal cancer and glioma, respectively.. Dietary phytoestrogens may play a role in survival from breast cancer ; evidence regarding other cancers is too limited to draw any conclusions.

    Topics: 4-Butyrolactone; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diet; Eating; Female; Humans; Isoflavones; Lignans; Male; Middle Aged; Neoplasms; Phytoestrogens; Young Adult

2021
Ellagic Acid and Schisandrins: Natural Biaryl Polyphenols with Therapeutic Potential to Overcome Multidrug Resistance in Cancer.
    Cells, 2021, 02-21, Volume: 10, Issue:2

    Multidrug resistance (MDR) is one of the major clinical challenges in cancer treatment and compromises the effectiveness of conventional anticancer chemotherapeutics. Among known mechanisms of drug resistance, drug efflux via ATP binding cassette (ABC) transporters, namely P-glycoprotein (P-gp) has been characterized as a major mechanism of MDR. The primary function of ABC transporters is to regulate the transport of endogenous and exogenous small molecules across the membrane barrier in various tissues. P-gp and similar efflux pumps are associated with MDR because of their overexpression in many cancer types. One of the intensively studied approaches to overcome this mode of MDR involves development of small molecules to modulate P-gp activity. This strategy improves the sensitivity of cancer cells to anticancer drugs that are otherwise ineffective. Although multiple generations of P-gp inhibitors have been identified to date, reported compounds have demonstrated low clinical efficacy and adverse effects. More recently, natural polyphenols have emerged as a promising class of compounds to address P-gp linked MDR. This review highlights the chemical structure and anticancer activities of selected members of a structurally unique class of 'biaryl' polyphenols. The discussion focuses on the anticancer properties of ellagic acid, ellagic acid derivatives, and schisandrins. Research reports regarding their inherent anticancer activities and their ability to sensitize MDR cell lines towards conventional anticancer drugs are highlighted here. Additionally, a brief discussion about the axial chirality (i.e., atropisomerism) that may be introduced into these natural products for medicinal chemistry studies is also provided.

    Topics: Animals; Cyclooctanes; Drug Discovery; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Ellagic Acid; Humans; Lignans; Neoplasms; Polycyclic Compounds; Polyphenols

2021
The legitimacy of using dietary supplement diglycoside secoisolariciresinol (SDG) from flaxseed in cancer.
    Roczniki Panstwowego Zakladu Higieny, 2021, Volume: 72, Issue:1

    Linseed, commonly known as flaxseed, is a fibre-rich food product. According to the recent study prepared by the American Institute for Cancer Research (AICR), an adequate intake of dietary fiber contributes to reducing the risk of colorectal cancer. In addition, the flaxseed and the oil extracted from it are considered to be food products with a high content of anti-inflammatory, unsaturated α-linolenic acid (ALA). However, the authors of the most recent scientific research have assigned the anticancer significance of flax seeds to plant lignan - secoisolariciresinol diglycoside (SDG), of which flaxseed is the main food source. This article provides a review of the world scientific literature together with an assessment of the validity of dietary supplementation with SDG from flaxseeds in cancer and during chemotherapeutic treatment. The paper also presents the European Food Safety Authority (EFSA) and the US Food and Drug Administration (FDA) view on dietary supplementation with flax seeds and its lignans. Additionally, selected dietary supplements available on the Polish market containing SDGs, linseed oil or linseed were analysed, together with a description of their intended use suggested by the manufacturers.

    Topics: Butylene Glycols; Dietary Supplements; Flax; Humans; Lignans; Neoplasms; Seeds

2021
Anticancer mechanisms of phytochemical compounds: focusing on epigenetic targets.
    Environmental science and pollution research international, 2021, Volume: 28, Issue:35

    It has recently been proven that epigenetic dysregulation is importantly involved in cell transformation and therefore induces cancerous diseases. The development of molecules called epidrugs, which target specifically different epigenetic modifications to restore cellular memory and therefore the treatment, became a real challenge currently. Currently, bioactive compounds of medicinal plants as epidrugs have been can identified and explored in cancer therapy. Indeed, these molecules can target specifically different epigenetic modulators including DNMT, HDAC, HAT, and HMT. Moreover, some compounds exhibit stochastic epigenetic actions on different pathways regulating cell memory. In this work, pharmacodynamic actions of natural epidrugs belonging to cannabinoids, carotenoids, chalcones, fatty acids, lignans, polysaccharides, saponins, secoiridoids, steroids, tannins, tanshinones, and other chemical classes we reported and highlighted. In this review, the effects of several natural bioactive compounds of epigenetic medications on cancerous diseases were highlighted. Numerous active molecules belonging to different chemical classes such as cannabinoids, carotenoids, fatty acids, lignans, polysaccharides, saponins, secoiridoids, steroids, tannins, and tanshinones are discussed in this review.

    Topics: Epigenesis, Genetic; Humans; Lignans; Neoplasms; Phytochemicals; Plants, Medicinal

2021
Arctigenin, an anti-tumor agent; a cutting-edge topic and up-to-the-minute approach in cancer treatment.
    European journal of pharmacology, 2021, Oct-15, Volume: 909

    Today, herbal-derived compounds are being increasingly studied in cancer treatment. Over the past decade, Arctigenin has been introduced as a bioactive dibenzylbutyrolactone lignan which is found in Chinese herbal medicines. In addition to anti-microbial, anti-inflammatory, immune-modulatory functions, Arctigenin has attracted growing attention due to its anti-tumor capabilities. It has been shown that Arctigenin can induce apoptosis and necrosis and abolish drug resistance in tumor cells by inducing apoptotic signaling pathways, caspases, cell cycle arrest, and the modulating proteasome. Moreover, Arctigenin mediates other anti-tumor functions through several mechanisms. It has been demonstrated that Arctigenin can act as an anti-inflammatory compound to inhibit inflammation in the tumor microenvironment. It also downregulates factors involved in tumor metastasis and angiogenesis, such as matrix metalloproteinases, N-cadherin, TGF-β, and VEGF. Additionally, Arctigenin, through modulation of MAPK signaling pathways and stress-related proteins, is able to abolish tumor cell growth in nutrient-deprived conditions. Due to the limited solubility of Arctigenin in water, it is suggested that modification of this compound through amino acid esterification can improve its pharmacogenetic properties. Collectively, it is hoped that using Arctigenin or its derivates might introduce new chemotherapeutic approaches in future treatment.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Disease Models, Animal; Drug Resistance, Neoplasm; Drugs, Chinese Herbal; Furans; Gene Expression Regulation, Neoplastic; Humans; Lignans; Neoplasms; Neovascularization, Pathologic; Signal Transduction; Xenograft Model Antitumor Assays

2021
Lignans from Medicinal Plants and their Anticancer Effect.
    Mini reviews in medicinal chemistry, 2020, Volume: 20, Issue:12

    Since early times, various plants have been used as remedies for treating different kinds of diseases and lesions with satisfying results. The phenolic compounds are secondary metabolites from medicinal plants which include a wide category of compounds such as phenolic acids, flavonoids, tannins, stilbenes, curcuminoids, xanthones, coumarins, lignans, etc. Between these, lignans are considered important in cancer prevention and treatment, besides other beneficial health effects, e.g. antioxidant, anticarcinogenic, antimutagenic, and anti-estrogenic effects. This review summarizes the most recent literature and the most important results concerning plant lignans and their derivatives in cancer prevention and treatment, both in vitro and in vivo assessments. The mechanistic aspects will be also highlighted.

    Topics: Antineoplastic Agents, Phytogenic; Cell Proliferation; Flax; Humans; Lignans; Medicine, Chinese Traditional; Neoplasms; Plants, Medicinal

2020
Biotechnological approaches to the production of plant-derived promising anticancer agents: An update and overview.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2020, Volume: 132

    The plant kingdom is a rich source of bioactive compounds, many of which have been used since pre-history for their therapeutic properties to treat a range of illnesses. These metabolites have recently attracted attention to their antineoplastic activities to treat various cancers relying on different mechanisms. Some of these molecules are glycosides, which have proven useful as anti-cancer agents, namely podophyllotoxin (PPT) anaryltetralin lignan or alkaloids. There are three primary forms of alkaloids, such as indole alkaloids (vincristine and vinblastine from Catharanthus roseus), quinoline alkaloid (camptothecin from Camptotheca acuminata), and diterpenoid alkaloid (taxol and it's analogous from Taxus and Corylus species). This review considers various plant biotechnology approaches used to enhance the production of these anticancer molecules in different species. In this regard, many in vitro culture techniques such as stimulation of suspension culture and hairy roots are being used to investigate the effects of plant growth regulators and elicitors on various explants.

    Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Biotechnology; Humans; Lignans; Neoplasms; Paclitaxel; Plants, Medicinal

2020
Anticancer and antimetastatic potential of enterolactone: Clinical, preclinical and mechanistic perspectives.
    European journal of pharmacology, 2019, Jun-05, Volume: 852

    Currently cancer is the second leading cause of death globally and worldwide incidence and mortality rates of all cancers of males and females are rising tremendously. In spite of advances in chemotherapy and radiation, metastasis and recurrence are considered as the major causes of cancer related deaths. Hence there is a mounting need to develop new therapeutic modalities to treat metastasis and recurrence in cancers. A significant amount of substantiation from epidemiological, clinical and laboratory research highlights the importance of diet and nutrition in cancer chemoprevention. Enterolactone (EL) is a bioactive phenolic metabolite known as a mammalian lignan derived from dietary lignans. Here in we review the reported anti-cancer properties of EL at preclinical as well as clinical level. Several in-vivo and in-vitro studies have provided strong evidence that EL exhibits potent anti-cancer and/or protective properties against different cancers including breast, prostate, colo-rectal, lung, ovarian, endometrial, cervical cancers and hepatocellular carcinoma. Reported laboratory studies indicate a clear role for EL in preventing cancer progression at various stages including cancer cell proliferation, survival, angiogenesis, inflammation and metastasis. In clinical settings, EL has been reported to reduce risk, decrease mortality rate and improve overall survival particularly in breast, prostate, colon, gastric and lung cancer. Further, the in-vitro human cell culture studies provide strong evidence of the anticancer and antimetastatic mechanisms of EL in several cancers. This comprehensive review supports an idea of projecting EL as a promising candidate for developing anticancer drug or adjunct dietary supplements and nutraceuticals.

    Topics: 4-Butyrolactone; Animals; Humans; Lignans; Neoplasm Metastasis; Neoplasms

2019
Honokiol for cancer therapeutics: A traditional medicine that can modulate multiple oncogenic targets.
    Pharmacological research, 2019, Volume: 144

    Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Humans; Lignans; Magnolia; Molecular Targeted Therapy; Neoplasms

2019
Dietary Flaxseed as a Strategy for Improving Human Health.
    Nutrients, 2019, May-25, Volume: 11, Issue:5

    Flaxseed is a rich source of the omega-3 fatty acid, alpha linolenic acid, the lignan secoisolariciresinol diglucoside and fiber. These compounds provide bioactivity of value to the health of animals and humans through their anti-inflammatory action, anti-oxidative capacity and lipid modulating properties. The characteristics of ingesting flaxseed or its bioactive components are discussed in this article. The benefits of administering flaxseed or the individual bioactive components on health and disease are also discussed in this review. Specifically, the current evidence on the benefits or limitations of dietary flaxseed in a variety of cardiovascular diseases, cancer, gastro-intestinal health and brain development and function, as well as hormonal status in menopausal women, are comprehensive topics for discussion.

    Topics: alpha-Linolenic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Butylene Glycols; Cardiovascular Diseases; Diet; Dietary Fiber; Dietary Supplements; Fatty Acids, Omega-3; Female; Flax; Functional Food; Gastrointestinal Diseases; Glucosides; Hormones; Humans; Lignans; Lipid Metabolism; Neoplasms; Seeds

2019
Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer.
    International journal of molecular sciences, 2018, 08-10, Volume: 19, Issue:8

    The past few decades have witnessed widespread research to challenge carcinogenesis; however, it remains one of the most important health concerns with the worst prognosis and diagnosis. Increasing lines of evidence clearly show that the rate of cancer incidence will increase in future and will create global havoc, designating it as an epidemic. Conventional chemotherapeutics and treatment with synthetic disciplines are often associated with adverse side effects and development of chemoresistance. Thus, discovering novel economic and patient friendly drugs that are safe and efficacious is warranted. Several natural compounds have proved their potential against this dreadful disease so far. Magnolol is a hydroxylated biphenyl isolated from the root and stem bark of Magnolia tree. Magnolol can efficiently prevent or inhibit the growth of various cancers originating from different organs such as brain, breast, cervical, colon, liver, lung, prostate, skin, etc. Considering these perspectives, the current review primarily focuses on the fascinating role of magnolol against various types of cancers, and the source and chemistry of magnolol and the molecular mechanism underlying the targets of magnolol are discussed. This review proposes magnolol as a suitable candidate that can be appropriately designed and established into a potent anti-cancer drug.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Humans; Lignans; Magnolia; Neoplasms

2018
Molecular mechanisms of the action of Arctigenin in cancer.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018, Volume: 108

    Since antediluvian times, the scientific community has realized that natural compounds exhibit enormous potential for the treatment of terrible diseases, such as cancer. Despite a variety of effective bioactive molecules, effective therapies still need to be developed to treat cancer. Hence, it is necessary to study the interactions of natural molecules with their cellular targets. Arctigenin (ATG), a natural lignan compound extracted from Arctium lappa, inhibits the growth of various cancer cells, such as those of the stomach, lungs, liver, and colon, as well as leukocytes, and regulates numerous intracellular activities, such as antioxidative, anti-inflammatory, and anticancer activities. The intention of this paper is to summarize and generally analyse the molecular pathways that are involved in the anticancer effects of ATG. In addition, the interactions of ATG with other drugs are also highlighted in this paper.

    Topics: Animals; Antineoplastic Agents; Antioxidants; Arctium; Furans; Humans; Lignans; Neoplasms

2018
Current detection technologies for circulating tumor cells.
    Chemical Society reviews, 2017, Apr-18, Volume: 46, Issue:8

    Circulating tumor cells (CTCs) are cancer cells that circulate in the blood stream after being naturally shed from original or metastatic tumors, and can lead to a new fatal metastasis. CTCs have become a hotspot research field during the last decade. Detection of CTCs, as a liquid biopsy of tumors, can be used for early diagnosis of cancers, earlier evaluation of cancer recurrence and chemotherapeutic efficacy, and choice of individual sensitive anti-cancer drugs. Therefore, CTC detection is a crucial tool to fight against cancer. Herein, we classify the currently reported CTC detection technologies, introduce some representative samples for each technology, conclude the advantages and limitations, and give a future perspective including the challenges and opportunities of CTC detection.

    Topics: Animals; Blood Circulation; Humans; Lignans; Limit of Detection; Nanostructures; Neoplasms; Neoplastic Cells, Circulating; Optical Imaging; Particle Size; Spectrum Analysis; Surface Properties

2017
A comprehensive review on the anti-cancer properties and mechanisms of action of sesamin, a lignan in sesame seeds (Sesamum indicum).
    European journal of pharmacology, 2017, Nov-15, Volume: 815

    Sesamin is the major active ingredient is Sesamum indicum seeds. Several studies revealed that sesamin possesses potent anti-cancer properties. The anti-cancer effects of sesamin have been mainly attributed to its anti-proliferative, pro-apoptotic, anti-inflammatory, anti-metastatic, anti- and pro-angiogenic, and pro-autophagocytic activities. In this review, we provide a comprehensive summary of the reported anti-cancer effects of sesamin, both in vitro and in vivo. Experimental findings related to the potential of sesamin to attenuate oxidative stress, inflammation, proliferation, metastasis, and angiogenesis in various cancer cells and tumors are analyzed. Studies focusing on the ability of sesamin to induce apoptosis and autophagy in cancer cells are also underscored. Moreover, the molecular mechanisms underlying the anti-cancer effects of sesamin are highlighted, and the major signaling pathways targeted by sesamin are identified. Although the exact signaling events triggered by sesamin in cancer cells are not fully revealed, our analysis indicates that NF-κB, STAT3, JNK, ERK1/2, p38 MAPK, PI3K/AKT, caspase-3, and p53 signaling pathways are critically involved in mediating the anti-cancer effects of sesamin. In sum, the experimental evidence suggesting that sesamin could exert potent anti-cancer activities in vitro and in vivo is compelling. Hence, sesamin can potentially be employed as an effective adjuvant therapeutic agent in ameliorating tumor development and progression, and therefore, it could be used in the prevention and/or treatment of various types of cancer.

    Topics: Animals; Antineoplastic Agents; Dioxoles; Humans; Lignans; Neoplasms; Seeds; Sesamum

2017
[Research progress in anticancer effects and molecular targets of honokiol in experimental therapy].
    Yao xue xue bao = Acta pharmaceutica Sinica, 2016, Volume: 51, Issue:2

    Honokiol(HNK), one of major biological active constituents of Mangnolia officinalis, exerts a wide range of biological functions, such as moderate anticancer effects. It inhibits the growth of lung cancer, gastrointestinal cancer, head and neck squamous cell carcinoma, breast cancer, prostate cancer, ovarian cancer, in vitro and in vivo through multiple potential molecular targets. It modulates apoptosis-associated signaling pathway, inhibits growth factor receptor-mediated signal transduction pathway, blocks nuclear factor-κB signaling pathway, decreases the expression level of androgen receptors, subsides m TOR and STAT3 signaling pathway, and so on. HNK enhances the inhibitory effects of traditional anticancer drugs or targeted antitumor drugs in vitro and in vivo. It reverses multidrug resistances of cancer cells to cisplatin, doxorubicin and paclitaxol. Therefore, HNK plays a role in the augmentation of antitumor effects of cancer drugs and the reversal of multidrug resistance of tumor cells. HNK is a promising biochemical modulator of anti-cancer medicines in the cancer therapy.

    Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Multiple; Drug Synergism; Humans; Lignans; Neoplasms; Signal Transduction; Therapies, Investigational

2016
Prevention and treatment of cancers by immune modulating nutrients.
    Molecular nutrition & food research, 2016, Volume: 60, Issue:6

    Epidemiological and laboratory data support the protective effects of bioactive nutrients in our diets for various diseases. Along with various factors, such as genetic history, alcohol, smoking, exercise, and dietary choices play a vital role in affecting an individual's immune responses toward a transforming cell, by either preventing or accelerating a neoplastic transformation. Ample evidence suggests that dietary nutrients control the inflammatory and protumorigenic responses in immune cells. Immunoprevention is usually associated with the modulation of immune responses that help in resolving the inflammation, thus improving clinical outcome. Various metabolic pathway-related nutrients, including glutamine, arginine, vitamins, minerals, and long-chain fatty acids, are important components of immunonutrient mixes. Epidemiological studies related to these substances have reported different results, with no or minimal effects. However, several studies suggest that these nutrients may have immune-modulating effects that may lower cancer risk. Preclinical studies submit that most of these components may provide beneficial effects. The present review discusses the available data, the immune-modulating functions of these nutrients, and how these substances could be used to study immune modulation in a neoplastic environment. Further research will help to determine whether the mechanistic signaling pathways in immune cells altered by nutrients can be exploited for cancer prevention and treatment.

    Topics: Animals; Arginine; Catechin; Cell Line, Tumor; Diet; Disease Models, Animal; Fatty Acids, Unsaturated; Glutamine; Humans; Isothiocyanates; Lignans; Meta-Analysis as Topic; Micronutrients; Neoplasms; Observational Studies as Topic; Phytochemicals; Polyphenols; Randomized Controlled Trials as Topic; Stilbenes

2016
HIF inhibitors for ischemic retinopathies and cancers: options beyond anti-VEGF therapies.
    Angiogenesis, 2016, Volume: 19, Issue:3

    Aberrant activation of the hypoxia inducible factor (HIF) pathway causing overexpression of angiogenic genes, like vascular endothelial growth factor (VEGF), is one of the underlying causes of ocular neovascularization (NV) and metastatic cancer. Consistently, along with surgical interventions, a number of anti-VEGF agents have been approved by FDA for the treatment of ocular neovascular diseases. These anti-VEGF agents, like ranibizumab/lucentis, have revolutionized the treatment in the past decade. However, substantial vision improvement is observed only in a subset of age-related macular degeneration patients receiving ranibizumab. Further, all current therapies are associated with limitations and side effects. For example, surgeries cause tissue destruction and inflammation while anti-VEGF therapies are expensive, require repeated administration, and offer temporary relief from vascular leakage. These factors impose significant cost and treatment burdens to both the patient and society. With an aging population in most western countries with a continually increasing number of patients on lifelong treatment for these retinal diseases, the focus of ocular drug development for neovascular diseases will be to improve efficacy while reducing treatment costs. Blocking the HIF pathway, a major regulator of ocular NV and cancer, offers an appealing therapeutic strategy. Therefore, this review summarizes HIF inhibitors that have been recently evaluated for the treatment of different cancers and ischemic retinopathies.

    Topics: Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Animals; Anthracyclines; Biphenyl Compounds; Cardiac Glycosides; Humans; Hypoxia-Inducible Factor 1; Indazoles; Lignans; Models, Biological; Neoplasms; Neovascularization, Pathologic; Retinal Neovascularization; Vascular Endothelial Growth Factors

2016
Honokiol targets mitochondria to halt cancer progression and metastasis.
    Molecular nutrition & food research, 2016, Volume: 60, Issue:6

    Cancer continues to be the leading cause of death worldwide. Plants have a long history of use in the treatment of cancer. Honokiol (HNK) is an important bioactive compound found in the bark of Magnolia tree, and has been shown to inhibit cancer growth and metastasis in many cell types in vitro and in animal models. Resistance to chemotherapy and radiotherapy is the major obstacle for cure of cancer. Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death, suggesting that HNK not only directly inhibits primary cancers and metastasis, but also has potential to overcome drug resistance. Ultimately, this may mean that HNK could be combined with traditional chemotherapies administered at lower doses to significantly reduce toxicity, meanwhile enhance efficacy. As a natural compound, HNK is composed of polyphenols and has been described in many studies targeting multiple key cell signaling molecules. Mitochondria are the main hub for cellular energy production and play an important role in cell survival, and are the key target identified for HNK to mediate cancer cell death, survival, and metastasis. In this review, we have summarized different aspects of HNK's anti-cancer effects from recent accumulated literature, as well as the underlying molecular mechanisms. This review is primarily focused on the effects of HNK on epidermal growth factor receptor (EGFR) and signal transduction and activator of transcription 3 (STAT3) signaling, as well as the broader regulation of mitochondrial function and cancer cell metabolism.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cell Line, Tumor; Disease Models, Animal; ErbB Receptors; Humans; Lignans; Magnolia; Mitochondria; Neoplasms; Plant Extracts; Polyphenols

2016
Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review.
    International journal of molecular sciences, 2016, Sep-22, Volume: 17, Issue:10

    Tocotrienol (T3), unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc). Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti-metastasis, nuclear factor-κB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the α-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of α-Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib) or dietary components (e.g., polyphenols, sesamin, and ferulic acid) exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy.

    Topics: Antineoplastic Agents; Catechin; Coumaric Acids; Dietary Supplements; Dioxoles; Drug Synergism; Drug Therapy, Combination; Humans; Lignans; Neoplasms; Resveratrol; Stilbenes; Tocotrienols

2016
Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs.
    Advances in experimental medicine and biology, 2016, Volume: 928

    Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cell Proliferation; Humans; Lignans; Neoplasms; Signal Transduction; Ultraviolet Rays

2016
In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: perspectives on cancer treatment.
    International journal of molecular sciences, 2015, Apr-24, Volume: 16, Issue:5

    Carcinogenesis is a multistep process triggered by genetic alterations that activate different signal transduction pathways and cause the progressive transformation of a normal cell into a cancer cell. Polyphenols, compounds ubiquitously expressed in plants, have anti-inflammatory, antimicrobial, antiviral, anticancer, and immunomodulatory properties, all of which are beneficial to human health. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis through direct interaction or modulation of gene expression, polyphenols can be employed to inhibit the growth of cancer cells. However, the main problem related to the use of polyphenols as anticancer agents is their poor bioavailability, which might hinder the in vivo effects of the single compound. In fact, polyphenols have a poor absorption and biodistribution, but also a fast metabolism and excretion in the human body. The poor bioavailability of a polyphenol will affect the effective dose delivered to cancer cells. One way to counteract this drawback could be combination treatment with different polyphenols or with polyphenols and other anti-cancer drugs, which can lead to more effective antitumor effects than treatment using only one of the compounds. This report reviews current knowledge on the anticancer effects of combinations of polyphenols or polyphenols and anticancer drugs, with a focus on their ability to modulate multiple signaling transduction pathways involved in cancer.

    Topics: Acids; Animals; Anthocyanins; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biological Availability; Carcinogenesis; Clinical Trials as Topic; Drug Screening Assays, Antitumor; Flavones; Flavonoids; Humans; Isoflavones; Lignans; Mice; Nanotechnology; Neoplasms; Phenols; Phosphorylation; Polyphenols; Rats; Signal Transduction; Stilbenes

2015
Honokiol analogs: a novel class of anticancer agents targeting cell signaling pathways and other bioactivities.
    Future medicinal chemistry, 2013, Volume: 5, Issue:7

    Honokiol (3,5-di-(2-propenyl)-1,1-biphenyl-2,2-diol) is a natural bioactive neolignan isolated from the genus Magnolia. In recent studies, honokiol has been observed to have anti-angiogenic, anticancer, anti-inflammatory, neuroprotective and GABA-modulating properties in vitro and in preclinical models. Honokiol and its analogs target multiple signaling pathways including NF-κB, STAT3, EGFR, mTOR and caspase-mediated common pathway, which regulate cancer initiation and progression. Honokiol and its targets of action may be helpful in the development of effective analogs and targeted cancer therapy. In this review, recent data describing the molecular targets of honokiol and its analogs with anticancer and some other bioactivities are discussed.

    Topics: Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Caspases; Humans; Lignans; Magnolia; Neoplasms; NF-kappa B; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Phospholipase D; Signal Transduction; Structure-Activity Relationship; TOR Serine-Threonine Kinases

2013
Anticancer drugs from traditional toxic Chinese medicines.
    Phytotherapy research : PTR, 2012, Volume: 26, Issue:10

    Many anticancer drugs are obtained from natural sources. Nature produces a variety of toxic compounds, which are often used as anticancer drugs. Up to now, there are at least 120 species of poisonous botanicals, animals and minerals, of which more than half have been found to possess significant anticancer properties. In spite of their clinical toxicity, they exhibit pharmacological effects and have been used as important traditional Chinese medicines for the different stages of cancer. The article reviews many structures such as alkaloids of Camptotheca acuminata, Catharanthus roseus and Cephalotaxus fortunei, lignans of Dysosma versipellis and Podophyllum emodi, ketones of Garcinia hanburyi, terpenoids of Mylabris and Ginkgo biloba, diterpenoids of Tripterygium wilfordii, Euphorbia fischeriana, Euphorbia lathyris, Euphorbia kansui, Daphne genkwa, Pseudolarix kaempferi and Brucea javanica, triterpenoids of Melia toosendan, steroids of Periploca sepium, Paris polyphylla and Venenum Bufonis, and arsenic compounds including Arsenicum and Realgar. By comparing their related phytochemistry, toxic effects and the recent advances in understanding the mechanisms of action, this review puts forward some ideals and examples about how to increase antitumour activity and/or reduce the side effects experienced with Chinese medicine.

    Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Drugs, Chinese Herbal; Humans; Ketones; Lignans; Medicine, Chinese Traditional; Neoplasms; Phytotherapy; Plants, Medicinal; Steroids; Terpenes

2012
Honokiol: a novel natural agent for cancer prevention and therapy.
    Current molecular medicine, 2012, Volume: 12, Issue:10

    Honokiol (3',5-di-(2-propenyl)-1,1'-biphenyl-2,4'-diol) is a bioactive natural product derived from Magnolia spp. Recent studies have demonstrated anti-inflammatory, anti-angiogenic, anti-oxidative and anticancer properties of honokiol in vitro and in preclinical models. Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR), which have great relevance during cancer initiation and progression. Furthermore, pharmacokinetic profile of honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials. In this review, we discuss recent data describing the molecular targets of honokiol and its anti-cancer activities against various malignancies in pre-clinical models. Evaluation of honokiol in clinical trials will be the next step towards its possible human applications.

    Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Cell Line, Tumor; ErbB Receptors; Humans; Lignans; Magnolia; Mice; Neoplasms; NF-kappa B; Plant Preparations; Rats; Signal Transduction; STAT3 Transcription Factor; TOR Serine-Threonine Kinases

2012
Phytochemicals and cancer risk: a review of the epidemiological evidence.
    Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2012, Volume: 27, Issue:5

    A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.

    Topics: Carotenoids; Flavonoids; Humans; Isothiocyanates; Lignans; Neoplasms; Phytotherapy; Plant Extracts; Plants

2012
Role of phytoestrogens in cancer therapy.
    Planta medica, 2010, Volume: 76, Issue:11

    Cancer is a leading cause of death worldwide, and the numbers of new cancer cases are expected to continue to rise. The main goals of cancer therapy include removing the primary tumor, preventing the spread of distant metastases, and improving survival and quality of life for the patients. To attain these goals of cancer therapy, the combination of different chemotherapeutics, as opposed to the conventional single-agent treatment, is an emerging area of research. Given the potential risks of drug toxicity in such treatment, the focus is to have a second compound that increases the anticancer potential of the primary agent but which reduces toxicity. There is an ever growing interest in treatment with natural compounds, such as plant phytoestrogens, as an adjuvant cancer therapy along with conventional cancer therapy. The question remains whether or not adding these compounds to the cancer therapy regimen as a second agent would be beneficial, and if they are safe to be used among cancer patients. The current literature suggests that phytoestrogen treatment is capable of inducing G2/M cell cycle arrest in a number of cancer cell lines, as well as upregulating cell cycle inhibitory molecules. Phytoestrogen therapy has been shown to inhibit inflammation, angiogenesis and metastases in various IN VIVO tumor models, and pronounced benefits have been observed when combined with radiation therapy. The lack of side effects from phase I and II clinical trials of phytoestrogens in cancer therapy points towards their safety, but to further understand their added benefit clinical studies with large sample sizes are required. We have reviewed the recent research studies in these areas in an attempt to find evidence for their role in cancer therapy as well as safety.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Cycle; Chemotherapy, Adjuvant; Humans; Inflammation; Isoflavones; Lignans; Mice; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Phytoestrogens; Randomized Controlled Trials as Topic

2010
Synthesis and biological activity of Wuweizisu C and analogs.
    Current topics in medicinal chemistry, 2009, Volume: 9, Issue:17

    Lignans are widely distributed in nature. The earliest recorded medicinal use of lignans dated back to over 1000 years ago. Lignan-rich plant products were also active ingredients in Chinese and Japanese folk medicines for the treatment of various diseases. The dried root and stem of this plant are listed in the Chinese pharmacopoeia for the treatment of rheumatoid arthritis, gastric, duodenal ulcers and many other diseases. This review highlights synthetic strategies for the Wuweizisu C analogs and the important pharmacological activities as well as therapeutic findings related to the treatment of HBV and other diseases. Notably a significant and ongoing project on Wuweizisu C and its analogs has led to the discovery and development of two potent derivatives alpha-DDB and BICYCLOL which are currently in clinical trials against HBV, especially in lowering elevated SGPT levels. Further design, synthesis, and evaluation of Wuweizisu C analogs are discussed.

    Topics: Acquired Immunodeficiency Syndrome; Animals; Antiviral Agents; Biological Products; Cyclooctanes; Hepatitis B; Humans; Lignans; Neoplasms; Polycyclic Compounds

2009
Berry fruits for cancer prevention: current status and future prospects.
    Journal of agricultural and food chemistry, 2008, Feb-13, Volume: 56, Issue:3

    Overwhelming evidence suggests that edible small and soft-fleshed berry fruits may have beneficial effects against several types of human cancers. The anticancer potential of berries has been related, at least in part, to a multitude of bioactive phytochemicals that these colorful fruits contain, including polyphenols (flavonoids, proanthocyanidins, ellagitannins, gallotannins, phenolic acids), stilbenoids, lignans, and triterpenoids. Studies show that the anticancer effects of berry bioactives are partially mediated through their abilities to counteract, reduce, and also repair damage resulting from oxidative stress and inflammation. In addition, berry bioactives also regulate carcinogen and xenobiotic metabolizing enzymes, various transcription and growth factors, inflammatory cytokines, and subcellular signaling pathways of cancer cell proliferation, apoptosis, and tumor angiogenesis. Berry phytochemicals may also potentially sensitize tumor cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance, and berry fruit consumption may provide protection from therapy-associated toxicities. Although a wide variety of berry fruits are consumed worldwide, this paper focuses on those commonly consumed in North America, namely, blackberries, black raspberries, blueberries, cranberries, red raspberries, and strawberries. In addition, a large body of studies on singly purified berry bioactives is available, but this paper focuses on studies of "whole berries" per se, that is, as berry extracts and purified fractions, juices, and freeze-dried powders. Potential mechanisms of anticancer action and bioavailability of berry phenolics, as well as gaps in knowledge and recommendations for future berry research, are also briefly discussed.

    Topics: Animals; Anticarcinogenic Agents; Biological Availability; Cell Line, Tumor; Diet; Female; Flavonoids; Fruit; Humans; Lignans; Male; Neoplasms; Phenols; Polyphenols; Stilbenes; Triterpenes

2008
[Interest of lignans in prevention and treatment of cancers].
    Medecine sciences : M/S, 2008, Volume: 24, Issue:5

    Lignans are diphenolic compounds widely distributed in the plant kingdom. They are mainly localised in lignified tissues, seeds and roots. These molecules are involved in plant defence mechanisms, but are also interesting for human health. Flax lignans belonging to the phytoestrogens are metabolised after ingestion into enterolignans that may offer a protection against the onset and development of hormono-dependant cancers. In vitro studies based on mammalian cellular models tend to confirm their beneficial effects observed during epidemiological studies and give us insights about their mechanisms of action. The most studied lignan, podophyllotoxin, and its semi-synthetic derivatives (etoposide, teniposide, etoposide phosphate), are particularly interesting at a curative level due to their cytotoxic properties. These semi-synthetic derivatives are used in chemotherapy of lung cancer for example. However, the extensive use of these anticancer drugs will lead to the problem of podophyllotoxin supply. This molecule is currently extracted from the rhizomes and roots of an Indian species Podophyllum hexandrum which has subsequently become endangered. Strategies are investigated to obtain economically viable alternative sources of Podophyllotoxin from plants and in vitro cultures of several species. Among them, north american Podophyllum peltatum, Linum wild species, Hyptis, Anthriscus, Juniperus or Dysosma species which accumulate Podophyllotoxin or closely related derivatives, are good candidates. double dagger.

    Topics: Anticarcinogenic Agents; Antineoplastic Agents; Humans; Lignans; Neoplasms; Phytoestrogens; Podophyllotoxin

2008
Flaxseed.
    Advances in food and nutrition research, 2006, Volume: 51

    Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus; Diet; Dietary Fiber; Flavonoids; Flax; Food Handling; Health Promotion; Hot Temperature; Humans; Lignans; Linseed Oil; Neoplasms; Nutritional Physiological Phenomena; Phenols; Plant Proteins; Polyphenols; Sensation

2006
Rye, lignans and human health.
    The Proceedings of the Nutrition Society, 2003, Volume: 62, Issue:1

    Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

    Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Fiber; Food, Organic; Humans; Lignans; Neoplasms; Secale

2003
Use of alternative therapies in menopause.
    Best practice & research. Clinical obstetrics & gynaecology, 2002, Volume: 16, Issue:3

    Hormone replacement therapy has traditionally been used to treat the accompanying symptoms of oestrogen deficiency in menopause. However, not all women can, or prefer to, receive this treatment and alternatives should be considered to reduce the increased risk of osteoporosis and heart disease in menopausal women. This chapter reviews the current literature on the efficacy of phyto-oestrogens in preventing cardiovascular disease, various cancers and osteoporosis, as well as treating the vasomotor and other menopause-related symptoms. Select herbal therapies, as well as selective oestrogen receptor modulators, are also considered.

    Topics: Cardiovascular Diseases; Estrogens; Female; Humans; Hypercholesterolemia; Isoflavones; Lignans; Menopause; Middle Aged; Neoplasms; Osteoporosis, Postmenopausal; Phytotherapy; Plant Preparations; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators

2002
Phyto-oestrogens and cancer.
    The Lancet. Oncology, 2002, Volume: 3, Issue:6

    Phyto-oestrogens have been suggested to have a preventive effect against various cancers. This review includes a discussion of the consumption of phyto-oestrogen-rich foods such as soy, a source of isoflavones, and whole grain products, which contain lignans, and their role in the prevention of breast, prostate, and colon cancer. In women, a soy-containing diet is only slightly protective against breast cancer, if at all, but is more likely to be beneficial if initiated before puberty or during adolescence. These findings are supported by conclusions of studies of immigrants and other epidemiological studies. However, in one case-control study and one prospective study, a low-lignan diet increased the risk of breast cancer. Experimental evidence also exists for an inhibitory effect of soy and rye bran on prostate-cancer growth and for rye bran or isolated lignans on colon cancer. Whether these observed protective effects are caused by the presence of dietary phyto-oestrogens, or whether they are merely indicators of a healthy diet in general, has not been established.

    Topics: 4-Butyrolactone; Animals; Breast Neoplasms; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lignans; Male; Neoplasms; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Tumor Cells, Cultured

2002
Protection against cancer by wheat bran: role of dietary fibre and phytochemicals.
    European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 1999, Volume: 8, Issue:1

    Human intervention and animal studies have shown that supplementing the diet with wheat bran can protect against the development of a range of cancers, especially those of the colon and breast. Wheat bran is a rich source of dietary fibres (plant cell walls) that have structures and compositions which indicate that they may protect against cancer. Nevertheless, dietary fibre makes up less than half of wheat bran. Other nutrients and phytochemicals are present in wheat bran, some of which may also protect against cancer. These include phytic acid and various phenolic components such as phenolic acids, lignans and flavonoids. A major goal of future research on wheat bran should be to determine the relative roles in cancer prevention of the different components in wheat bran.

    Topics: Animals; Anticarcinogenic Agents; Breast Neoplasms; Colonic Neoplasms; Dietary Fiber; Disease Models, Animal; Female; Flavonoids; Humans; Hydroxybenzoates; Lignans; Neoplasms; Phytic Acid; Triticum

1999
Plant lignans and health: cancer chemoprevention and biotechnological opportunities.
    Basic life sciences, 1999, Volume: 66

    Topics: Animals; Anticarcinogenic Agents; Biotechnology; Diet; Humans; Lignans; Mammals; Neoplasms; Vegetables

1999
Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence.
    The Journal of clinical endocrinology and metabolism, 1998, Volume: 83, Issue:7

    Phytoestrogens represent a family of plant compounds that have been shown to have both estrogenic and antiestrogenic properties. A variety of these plant compounds and their mammalian metabolic products have been identified in various human body fluids and fall under two main categories: isoflavones and lignans. A wide range of commonly consumed foods contain appreciable amounts of these different phytoestrogens. For example, soy and flax products are particularly good sources of isoflavones and lignans, respectively. Accumulating evidence from molecular and cellular biology experiments, animal studies, and, to a limited extent, human clinical trials suggests that phytoestrogens may potentially confer health benefits related to cardiovascular diseases, cancer, osteoporosis, and menopausal symptoms. These potential health benefits are consistent with the epidemiological evidence that rates of heart disease, various cancers, osteoporotic fractures, and menopausal symptoms are more favorable among populations that consume plant-based diets, particularly among cultures with diets that are traditionally high in soy products. The evidence reviewed here will facilitate the identification of what is known in this area, the gaps that exist, and the future research that holds the most potential and promise.

    Topics: Cardiovascular Diseases; Diet; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Lignans; Male; Neoplasms; Osteoporosis; Plants, Edible

1998
Experimental studies on lignans and cancer.
    Bailliere's clinical endocrinology and metabolism, 1998, Volume: 12, Issue:4

    Mammalian lignans are produced from plant precursors such as secoisolariciresinol diglycoside (SDG) and matairesinol via the action of bacteria in the human or animal colon. While precursors are found in many plant foods, flaxseed is the richest source of SDG and was therefore used as a model to determine the anti-cancer effects of lignans. This paper reviews the experimental studies in animals and humans demonstrating the anti-cancer effects of flaxseed and its SDG as well as other studies relevant to the clinical use of lignans, such as those on their food sources, bio-availability and safety.

    Topics: Animals; Biological Availability; Female; Food; Humans; Lignans; Neoplasms

1998
Whole-grain consumption and chronic disease: protective mechanisms.
    Nutrition and cancer, 1997, Volume: 27, Issue:1

    Dietary guidance recommends consumption of whole grains to reduce the risk of chronic diseases including cancer and cardiovascular disease. Epidemiologic studies support the belief that whole grains are protective against cancers, especially gastrointestinal cancers such as gastric and colonic, and cardiovascular disease. Components in whole grains that may be protective are diverse and include compounds that affect the gut environment, i.e., dietary fiber, resistant starch, and other undigestible compounds in whole grains, compounds that function as antioxidants such as trace minerals and phenolic compounds, and compounds that are phytoestrogens with potential hormonal effects. Many of the protective compounds in whole grains are also in fruits and vegetables, but some plant compounds are more concentrated in whole grains, such as phenolic compounds including ferulic and caffeic acid. Other potential mechanistic effects of whole grains include binding of carcinogens and modulation of glycemic index. Clearly, the range of protective substances in whole grains is impressive, and advice to consume additional whole grains is justifiable.

    Topics: Acute Disease; Antioxidants; Cardiovascular Diseases; Dietary Fiber; Eating; Edible Grain; Estrogens, Non-Steroidal; Humans; Intestine, Large; Isoflavones; Lignans; Models, Biological; Neoplasms; Nutritional Requirements; Phytoestrogens; Plant Preparations; Risk Factors; Starch

1997
Phyto-oestrogens and Western diseases.
    Annals of medicine, 1997, Volume: 29, Issue:2

    Incidences of breast, colorectal and prostate cancer are high in the Western world compared to countries in Asia. We have postulated that the Western diet compared to the semivegetarian diet in some Asian countries may alter hormone production, metabolism or action at the cellular level by some biochemical mechanisms. Our interest has been focused on two groups of hormone-like diphenolic phyto-oestrogens of dietary origin, the lignans and isoflavonoids abundant in plasma of subjects living in areas with low cancer incidence. The precursors of the biologically active compounds detected in man are found in soybean products, whole-grain cereal food, seeds, and berries. The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds. The weakly oestrogenic diphenols formed influence sex-hormone production, metabolism and biological activity, intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, cell adhesion and angiogenesis in such a way as to make them strong candidates for a role as natural cancer-protective compounds. Their effect on some of the most important steroid biosynthetic enzymes may result in beneficial modulation of hormone concentrations and action in the cells preventing development of cancer. Owing to their oestrogenic activity they reduce hot flushes and vaginal dryness in postmenopausal women and may to some degree inhibit osteoporosis, but alone they may be insufficient for complete protection. Soy intake prevents oxidation of the low-density lipoproteins in vitro when isolated from soy-treated individuals and affect favourably plasma lipid concentrations. Animal experiments provide evidence suggesting that both lignans and isoflavonoids may prevent the development of cancer as well as atherosclerosis. However, in some of these experiments it has not been possible to separate the phyto-oestrogen effect from the effect of other components in the food. The isoflavonoids and lignans may play a significant inhibitory role in cancer development particularly in the promotional phase of the disease, but recent evidence points also to a role in the initiation stage of carcinogenesis. At present, however, no definite recommendations can be made as to the dietary amounts needed for prevention of disease. This review deals with all the above-mentioned aspects of phyto-oestrogens.

    Topics: Diet; Estrogens; Female; Heart Diseases; Humans; Lignans; Male; Menopause; Neoplasms; Osteoporosis; Plant Growth Regulators; Plants, Edible; Western World

1997
A review of the clinical effects of phytoestrogens.
    Obstetrics and gynecology, 1996, Volume: 87, Issue:5 Pt 2

    To review the sources, metabolism, potencies, and clinical effects of phytoestrogens on humans.. The MEDLINE data base for the years 1980-1995 and reference lists of published articles were searched for relevant English-language articles concerning phytoestrogens, soy products, and diets with high-phytoestrogen content.. We identified 861 articles as being relevant. Human cell line studies, human epidemiologic studies (case-control or cohort), randomized trials, and review articles were included. Animal studies regarding phytoestrogens were included when no human data were available concerning an important clinical area.. Included were studies containing information considered pertinent to clinical practice in the areas of growth and development, menopause, cancer, and cardiovascular disease. When findings varied, those presented in this study reflect consensus. All studies concurred that phytoestrogens are biologically active in humans or animals. These compounds inhibit the growth of different cancer cell lines in cell culture and animal models. Human epidemiologic evidence supports the hypothesis that phytoestrogens inhibit cancer formation and growth in humans. Foods containing phytoestrogens reduce cholesterol levels in humans, and cell line, animal, and human data show benefit in treating osteoporosis.. This review suggests that phytoestrogens are among the dietary factors affording protection against cancer and heart disease in vegetarians. With this epidemiologic and cell line evidence, intervention studies are now an appropriate consideration to assess the clinical effects of phytoestrogens because of the potentially important health benefits associated with the consumption of foods containing these compounds.

    Topics: Animals; Cardiovascular Diseases; Climacteric; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lignans; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Tumor Cells, Cultured

1996
Soybean phytoestrogen intake and cancer risk.
    The Journal of nutrition, 1995, Volume: 125, Issue:3 Suppl

    Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.

    Topics: Animals; Antineoplastic Agents; Diet; Estrogens; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Incidence; Isoflavones; Lignans; Male; Neoplasms; Phytoestrogens; Plant Preparations; Risk Factors

1995
Phytoestrogens: epidemiology and a possible role in cancer protection.
    Environmental health perspectives, 1995, Volume: 103 Suppl 7

    Because many diseases of the Western Hemisphere are hormone-dependent cancers, we have postulated that the Western diet, compared to a vegetarian or semivegetarian diet, may alter hormone production, metabolism, or action at the cellular level by some biochemical mechanisms. Recently, our interest has been mainly focused on the cancer-protective role of some hormonelike diphenolic phytoestrogens of dietary origin, the lignans and the isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids), whole grain cereal food, seeds, and probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormonelike compounds with weak estrogenic but also antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, and angiogenesis in a way that makes them strong candidates for a role as natural cancer-protective compounds. Epidemiologic investigations strongly support this hypothesis because the highest levels of these compounds in the diet are found in countries or regions with low cancer incidence. This report is a review on recent results suggesting that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.

    Topics: Anticarcinogenic Agents; Estrogens; Female; Humans; Isoflavones; Lignans; Male; Neoplasms; Plant Growth Regulators; Plants, Edible; Sex Hormone-Binding Globulin

1995
Antioxidants and hormone-mediated health benefits of whole grains.
    Critical reviews in food science and nutrition, 1994, Volume: 34, Issue:5-6

    Lignans and phytoestrogens have been associated with protective effect against hormone-related diseases, for example, cancer of the breast and prostate, and potential mechanisms for this effect have been reported. Antioxidants also appear to have some protective effect against diseases associated with reactive free radicals such as coronary heart disease and cancer. Whole grains contain some of these substances particularly the mammalian lignan precursors, vitamin E, other phenolic compounds, Se, and phytic acid. These substances may in part be responsible for the reduced risk of cancer and coronary heart disease associated with intake of high-fiber diets containing whole grains. Because they are more associated with the fiber in the outer layers of the grain, the intake of whole vs. refined grain is emphasized for optimum health benefits.

    Topics: Antioxidants; Edible Grain; Estrogens; Estrogens, Non-Steroidal; Health Promotion; Heart Diseases; Hormones; Humans; Isoflavones; Lignans; Neoplasms; Phytoestrogens; Plant Preparations

1994

Other Studies

58 other study(ies) available for lignans and Neoplasms

ArticleYear
Dietary phytoestrogens and total and cause-specific mortality: results from 2 prospective cohort studies.
    The American journal of clinical nutrition, 2023, Volume: 117, Issue:1

    Evidence regarding dietary phytoestrogens in relation to mortality remains limited.. The objective of the study is to examine the associations of intake of isoflavones, lignans, and coumarins with total and cause-specific mortality in US males and females.. We followed 75,981 females in the Nurses' Health Study (1984-2018) and 44,001 males in the Health Professionals Follow-up Study (1986-2018), who were free of cardiovascular disease (CVD), diabetes, or cancer at baseline. Their diet was repeatedly assessed using validated food frequency questionnaires every 2-4 y. Associations with mortality were assessed using time-dependent Cox models with adjustments for demographics, dietary and lifestyle factors, and medical history.. During 3,427,156 person-years of follow-up, we documented 50,734 deaths, including 12,492 CVD deaths, 13,726 cancer deaths, and 24,516 other non-CVD and noncancer deaths. After multivariable adjustment, the higher total phytoestrogen intake was associated with lower risk of total CVD and other non-CVD and noncancer mortality: comparing extreme quintiles, the pooled HRs (95% CIs) were 0.89 (0.87, 0.92), 0.90 (0.85, 0.96), and 0.86 (0.82, 0.90), respectively. We did not find a significant association with cancer mortality [0.97 (0.92, 1.03)]. For individual phytoestrogens in relation to total mortality, the pooled HRs (95% CIs) comparing extreme quintiles were 0.90 (0.87, 0.92) for isoflavones, 0.93 (0.90, 0.96) for lignans, and 0.93 (0.90, 0.95) for coumarins. Individual phytoestrogens were also significantly associated with lower risk of CVD mortality and other types of mortality. Primary food sources of phytoestrogens, including tofu, soy milk, whole grains, tea, and flaxseed, were also inversely associated with total mortality.. A higher intake of total phytoestrogens, including isoflavones, lignans, and coumarins, and foods rich in these compounds was associated with lower risk of total and certain cause-specific mortality in generally healthy US adults. These data suggest that these phytochemicals and their dietary sources may be integrated into an overall healthy diet to achieve a longer life span.

    Topics: Adult; Cardiovascular Diseases; Cause of Death; Coumarins; Diet; Female; Follow-Up Studies; Humans; Isoflavones; Lignans; Male; Neoplasms; Phytoestrogens; Prospective Studies

2023
SAR study culminates in a series of HDAC6 selective inhibitors featuring Schisandrin C-analogous Cap as potential immunomodulatory agents for cancer therapy.
    Bioorganic chemistry, 2022, Volume: 127

    HDAC6 inhibitors (HDAC6is) represent an emerging therapeutic option for triggering anti-cancer immune response. In this work, a novel series of HDAC6is, derived from an in-house analog of the traditional Chinese medicine monomer Schisandrin C, were designed and synthesized for SAR study. Throughout the 29 target compounds, 24a, 24b and 24h exerted single-digit nanomolar enzymatic activity and remarkably elevated subtype selectivity compared to the clinically investigated HDAC6i Ricolinostat (Selectivity index = 3.3). In A549 tumor cells, 24h, as the representative in this series (IC

    Topics: Animals; Antineoplastic Agents; Cyclooctanes; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Humans; Immunomodulating Agents; Lignans; Neoplasms; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship

2022
A co-delivery nanoplatform for a lignan-derived compound and perfluorocarbon tuning IL-25 secretion and the oxygen level in tumor microenvironments for meliorative tumor radiotherapy.
    Nanoscale, 2021, Aug-28, Volume: 13, Issue:32

    A hypoxic environment in tumors hampers the therapeutic efficacy of radiotherapy. Moreover, radiotherapy, a localized treatment technique, can barely control tumor metastases. Herein, poly(lactic-co-glycolic acid) was used to encapsulate perfluorocarbon (PFC) for increasing the oxygen level and a lignan-derived compound (Q1) for enhancing IL-25 secretion from fibroblasts, thereby boosting the radiotherapeutic effect on local and distant tumors. The prepared co-delivery nanoplatform, PFC-Q1@PLGA, has a nano-scale size of around 160 nm and a negative zeta potential (about -13 mV). PFC-Q1@PLGA treatment leads to an arrest of the G2 phase (4n) in the cell cycle and reduces the mitochondria membrane potential. A high expression level of IL-25 in fibroblasts is detected after the cells are treated with PFC-Q1@PLGA, which increases the late apoptosis percentage of 4T1 cells after treatment with IL-25-containing conditional medium from fibroblasts. The oxygen level in tumors is significantly promoted to about 52.3% after injection of oxygen-saturated PFC-Q1@PLGA (O

    Topics: Animals; Fluorocarbons; Lignans; Mice; Nanoparticles; Neoplasms; Oxygen; Tumor Microenvironment

2021
Synthesis and in vitro antitumor evaluation of honokiol derivatives.
    Bioorganic & medicinal chemistry letters, 2020, 01-15, Volume: 30, Issue:2

    Honokiol is a natural bioactive neolignan and has been widely researched and structural modified as an anticancer agent. In this paper, 18 honokiol derivatives were synthesized and investigated for their antitumor activity. Among these, the promising compound 5a exhibited much higher anti-proliferative activity with IC

    Topics: Antineoplastic Agents; Biphenyl Compounds; Humans; Lignans; Neoplasms

2020
Inhibition of autophagy sensitizes lignan-induced endoplasmic reticulum stress-mediated cell death.
    Biochemical and biophysical research communications, 2020, 05-28, Volume: 526, Issue:2

    Relationship between autophagy and endoplasmic reticulum (ER) stress and their application to treat cancer have been actively studied these days. Recently, a lignan [(-)-(2R, 3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica has been found to reduce the viability of colon cancer cells. In this study, we have observed DFS-induced autophagy in a variety of cancer cell lines. In addition, DFS led to ER stress, based on the activation of unfolded protein response (UPR) transducers and an elevated expression of UPR target genes in prostate and colon cancer cells. Further investigation has shown that DFS triggered the activation of AMP-activated protein kinase (AMPK) signaling and nuclear translocation of transcription factor EB (TFEB). Furthermore, the cytotoxicity of DFS was potentiated by the co-treatment of autophagy inhibitor in these cancer cells. This study has provided a noble implication that the combination of DFS and autophagy inhibition exerts a synergistic effect in cancer treatment.

    Topics: Alnus; AMP-Activated Protein Kinases; Antineoplastic Agents, Phytogenic; Autophagy; Cell Death; Cell Line, Tumor; Endoplasmic Reticulum Stress; Humans; Lignans; Neoplasms; Unfolded Protein Response

2020
Magnolol inhibits myotube atrophy induced by cancer cachexia through myostatin signaling pathway in vitro.
    Journal of natural medicines, 2020, Volume: 74, Issue:4

    Cancer cachexia is a complex and multifactorial syndrome that influences about 50-80% of cancer patients and may lead to 20% of cancer deaths and muscle atrophy is the key characteristic of the syndrome. Recent researches have shown that myostatin is a negative regulator in the growth and differentiation of skeletal muscle. Herein, C2C12 cancer cachexia model was established with C26 conditioned culture medium (CCM), then treated with magnolol to evaluate the pharmacological activity of magnolol in myotube atrophy. Our results demonstrated that magnolol inhibited the activity of myostatin promotor and the myostatin signaling pathway. In C2C12 cancer cachexia model, magnolol decreased myostatin expression, inhibited the phosphorylation of SMAD2/3 activated by C26 conditioned culture medium (CCM), and elevated the phosphorylation of FOXO3a lowered by CCM. Myosin heavy chain (MyHC), myogenin (MyoG), and myogenic differentiation (MyoD), as three common myotube markers in C2C12 myotube, were decreased by CCM, which could be effectively reversed by magnolol via activation of AKT/mTOR-regulated protein synthesis and inhibition of ubiquitin-mediated proteolysis. This study reveals that magnolol inhibits myotube atrophy induced by CCM by increasing protein synthesis and decreasing ubiquitin-mediated proteolysis, so that magnolol is a promising leading compound in treating muscle atrophy induced by cancer cachexia.

    Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Products; Biphenyl Compounds; Cachexia; Cell Line, Tumor; Humans; Lignans; Mice; Muscle Fibers, Skeletal; Muscular Atrophy; Myostatin; Neoplasms; Transfection

2020
Lignans and Neolignans with Antioxidant and Human Cancer Cell Proliferation Inhibitory Activities from
    Journal of agricultural and food chemistry, 2020, Aug-19, Volume: 68, Issue:33

    In the aim to evaluate the functional food property of

    Topics: Antioxidants; Cell Line, Tumor; Cell Proliferation; Cinnamomum; Functional Food; Growth Inhibitors; Humans; Lignans; Molecular Structure; Neoplasms; Plant Extracts

2020
Magnolol Enhances the Therapeutic Effects of TRAIL through DR5 Upregulation and Downregulation of c-FLIP and Mcl-1 Proteins in Cancer Cells.
    Molecules (Basel, Switzerland), 2020, Oct-08, Volume: 25, Issue:19

    Magnolol is a biologically active compound, isolated from the Chinese herb

    Topics: A549 Cells; Apoptosis; Biphenyl Compounds; CASP8 and FADD-Like Apoptosis Regulating Protein; Cell Line, Tumor; Cell Proliferation; Down-Regulation; HeLa Cells; Humans; Lignans; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasms; Proteasome Endopeptidase Complex; Receptors, TNF-Related Apoptosis-Inducing Ligand; TNF-Related Apoptosis-Inducing Ligand; Up-Regulation

2020
Anticancer activity of gomisin J from Schisandra chinensis fruit.
    Oncology reports, 2019, Volume: 41, Issue:1

    In attempting to identify effective anticancer drugs from natural products that are harmless to humans, we found that the gomisin J from Schisandra chinensis fruit has anticancer activity. Schisandra chinensis fruits are used in traditional herbal medicine and gomisin J is one of their chemical constituents. In the present study, we examined the anticancer activity of gomisin J in MCF7 and MDA-MB-231 breast cancer cell lines and in MCF10A normal cell line, in a time- and concentration-dependent manner. Our data revealed that gomisin J exerted a much stronger cytotoxic effect on MCF7 and MDA-MB-231 cancer cells than on MCF10A normal cells. Gomisin J suppressed the proliferation and decreased the viability of MCF7 and MDA-MB-231 cells at relatively low (<10 µg/ml) and high (>30 µg/ml) concentrations, respectively. Our data also revealed that gomisin J induced necroptosis, a programmed form of necrosis, as well as apoptosis. Notably, gomisin J predominantly induced necroptosis in MCF7 cells that are known to have high resistance to many pro-apoptotic anticancer drugs, while MDA-MB-231 exhibited a much lower level of necroptosis but instead a higher level of apoptosis. This data indicated the possibility that it may be used as a more effective anticancer drug, especially in apoptosis-resistant malignant cancer cells. In an extended study, gomisin J exhibited a strong cytotoxic effect on all tested various types of 13 cancer cell lines, indicating its potential to be used against a wide range of different types of cancer cells.

    Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Fruit; Humans; Lignans; Neoplasms; Polycyclic Compounds; Schisandra

2019
The effects of Arctigenin-Valine ester on chemotherapy-induced myelosuppression in mice.
    Bioorganic & medicinal chemistry, 2019, 06-15, Volume: 27, Issue:12

    To explore whether Arctigenin-Valine ester (ARG-V) can treat myelosuppression caused by chemotherapy.. The number of peripheral blood cells of the mice was measured by an automatic blood analyzer, and the hematopoietic progenitor colonies CFU-GM, CFU-E, BFU-E, and CFU-Meg were cultured in vitro. Hematopoietic progenitor colonies and BMNCs were counted under an inverted microscope. The expressions of cytokines GM-CSF, EPO and TPO were detected by ELISA. The cell cycle was measured by flow cytometry. The expressions of related proteins MEK and p-ERK were quantitated by western blots, and the thymus index and spleen index were quantitated.. After taking ARG-V, the peripheral blood cells of the mice gradually returned to normal, the number of nucleated cells in the bone marrow increased, the thymus index increased, the spleen index decreased, the number of hematopoietic progenitor cells increased, and the hematopoietic cytokines decreased. And ARG-V promoted the transformation of myelosuppression cells from G0/G1 to S and from S to G2/M. ARG-V could up-regulate the expression of MEK and p-ERK, and low dose ARG-V is not as effective in all aspects as high dose ARG-V.. ARG-V can effectively alleviate the myelosuppression that caused by intraperitoneal injection of CTX in 100mg/kg, and ARG-V can promote the proliferation and differentiation of hematopoietic progenitor cells and improve immunity, and the effect of high-dose Arctigenin-Valine ester is more significant to some extent.

    Topics: Animals; Antineoplastic Agents; Bone Marrow Cells; Cell Cycle Checkpoints; Cytokines; Furans; Hematopoietic Stem Cells; Lignans; Male; Mice; Mice, Inbred BALB C; Neoplasms; Valine

2019
Pre-diagnostic plasma enterolactone concentrations are associated with lower mortality among individuals with type 2 diabetes: a case-cohort study in the Danish Diet, Cancer and Health cohort.
    Diabetologia, 2019, Volume: 62, Issue:6

    The phytoestrogen enterolactone is a gut microbiota-derived metabolite of plant lignans with suggested beneficial properties for health. In the current study, we investigated the association between pre-diagnostic plasma enterolactone concentrations and mortality among individuals diagnosed with type 2 diabetes.. In a population of people diagnosed with diabetes, nested within the Danish Diet, Cancer and Health cohort, we conducted a case-cohort study including a random sample of n = 450 cases (deceased) and a randomly selected subcohort of n = 850 (in total n = 617 deaths). Information on diagnosis, vital status and cause of death was obtained from Danish registers. Cox proportional hazard models with special weighting were applied to assess all-cause and cause-specific mortality.. The median enterolactone concentration of the current population was low, 10.9 nmol/l (5th percentile to 95th percentile: 1.3-59.6), compared with previously reported concentrations from the Diet, Cancer and Health cohort. Pre-diagnostic enterolactone concentrations were associated with lower all-cause mortality when assessed linearly per doubling in concentration (log. Based on this large cohort of people with diabetes with detailed and complete baseline and follow-up information, pre-diagnostic enterolactone concentrations were inversely associated with mortality. To our knowledge, this is the first study on enterolactone and type 2 diabetes mortality. Our findings call for further exploration of enterolactone in type 2 diabetes management.

    Topics: 4-Butyrolactone; Aged; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Lignans; Male; Middle Aged; Neoplasms; Prognosis; Random Allocation

2019
Anticancer activity of synthetic (±)-kusunokinin and its derivative (±)-bursehernin on human cancer cell lines.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2019, Volume: 117

    Topics: Antineoplastic Agents; Caspases; Cell Cycle; Cell Death; Cell Line, Tumor; Humans; Inhibitory Concentration 50; Lactones; Lignans; Models, Biological; Neoplasm Proteins; Neoplasms

2019
Experimental study of the anti-tumour activity and pharmacokinetics of arctigenin and its valine ester derivative.
    Scientific reports, 2018, 02-19, Volume: 8, Issue:1

    Arctigenin (ARG) is a functional active component that has important physiological and pharmacological activities. The anti-tumour and anti-inflammatory activities of ARG show good potential for application and development, but this material has the defect of low water solubility. In this experiment, the valine derivative of ARG (ARG-V) was designed and synthesized to overcome this disadvantage. The ARG amino acid, EDCI and DMAP were raw materials in the addition reaction, with a molar ratio of 1:2:2:0.5. The yield of ARG-V was up to 80%. ARG-V has strong anti-tumour activity in vivo and in vitro. The inhibitory rate of ARG-V was 69.2%, with less damage to the immune organs and different degrees of increased serum cytotoxicity. Moreover, the pharmacokinetics of ARG following oral administration and ARG-V following oral administration in rats were also studied. The C

    Topics: Administration, Oral; Animals; Biological Availability; Cell Proliferation; Esters; Furans; Humans; Lignans; Mice; Mice, Inbred ICR; Neoplasms; Rats; Rats, Wistar; Solubility

2018
Structure-guided cancer blockade between bioactive bursehernin and proteins: Molecular docking and molecular dynamics study.
    Journal of molecular graphics & modelling, 2017, Volume: 74

    Bursehernin (5'-desmethoxyyatein) is a natural lignan, which has anti-tumor activity in vitro. In this study, the binding-inhibitory effects of bursehernin were screening on selected 80 proteins associated with cancer pathway. The computational analysis suggested inhibitory effect due to bursehernin towards proteins related to cancer proliferation, including FMS kinase receptor, heat shock protein 90-α (Hsp90-α), adenylate cyclase 10 (ADCY10), mitogen-activated protein kinase kinase (MEK1), and α-tubulin. Moreover, bursehernin could interfere with cell cycle progression via binding to cyclin B proteins. Among all screened proteins, the compound showed an interesting binding affinity to the FMS kinase receptor. The binding mode studies by molecular dynamic technique showed that aromatic ring of bursehernin compound was responsible for compound-protein interaction through pi-pi stacking with Tyr105 and Phe178 of the FMS kinase receptor. This study suggests that bursehernin has potential for development as an anti-tumor agent with an anti-proliferation, and cell cycle arrest inducing, although further studies are needed.

    Topics: Antineoplastic Agents; Binding Sites; Humans; Lactones; Lignans; Molecular Docking Simulation; Molecular Dynamics Simulation; Neoplasm Proteins; Neoplasms; Protein Binding; Protein Conformation, alpha-Helical; Protein Domains; Thermodynamics

2017
Mechanism and Anticancer Activity of the Metabolites of an Endophytic Fungi from Eucommia ulmoides Oliv.
    Anti-cancer agents in medicinal chemistry, 2017, Volume: 17, Issue:7

    Backgroud: Pinoresinol (Pin) and pinoresinol monoglucoside (PMG) are plant-derived lignan molecules with multiple functions. We showed previously that an endophytic fungus from Eucommia ulmoides Oliv., Phomopsis sp. XP-8 is able to produce Pin and PMG.. This study was carried out to test the anti-tumor capability of the culture of XP-8 and identify the major effective compounds.. The fungal culture was added in the culture of HepG2 and K562 cells, and the viabilities of these cells were detected and the possible mechanism was analyzed.. The fungal culture showed significant capaiblity in decreasing the viability of tumor cells and induce apoptosis via up-regulation of the expression of apoptosis-related genes. It also significantly inhibited the adhesion and migration of HepG2 cells by blocking MMP-9 expression. Pin and PMG were isolated from the growth culture and shown to be the major effective components for inhibition.. The study indicated the potential application of XP-8 in the production of anti-tumour products by the bioconversion of glucose.

    Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Movement; Endophytes; Eucommiaceae; Fungi; Furans; Gene Expression Regulation, Neoplastic; Humans; Lignans; Neoplasms

2017
Urinary phytoestrogens and cancer, cardiovascular, and all-cause mortality in the continuous National Health and Nutrition Examination Survey.
    European journal of nutrition, 2016, Volume: 55, Issue:3

    Experimental studies suggest that phytoestrogen intake alters cancer and cardiovascular risk. This study investigated the associations of urinary phytoestrogens with total cancer (n = 79), cardiovascular (n = 108), and all-cause (n = 290) mortality among 5179 participants in the continuous National Health and Nutrition Examination Survey (1999-2004).. Urinary phytoestrogens were measured using high-performance liquid chromatography with tandem mass spectrometric detection. Survival analysis was performed to evaluate hazard ratios (HRs) and 95 % confidence intervals (CIs) for each of the three outcomes in relation to urinary phytoestrogens.. After adjustment for confounders, higher urinary concentrations of total enterolignans were associated with a reduced risk of death from cardiovascular disease (HR for tertile 3 vs. tertile 1 0.48; 95 % CI 0.24, 0.97), whereas higher urinary concentrations of total isoflavones (HR for tertile 3 vs. tertile 1 2.14; 95 % CI 1.03, 4.47) and daidzein (HR for tertile 3 vs. tertile 1 2.05; 95 % CI 1.02, 4.11) were associated with an increased risk. A reduction in all-cause mortality was observed for elevated urinary concentrations of total enterolignans (HR for tertile 3 vs. tertile 1 0.65; 95 % CI 0.43, 0.96) and enterolactone (HR for tertile 3 vs. tertile 1 0.65; 95 % CI 0.44, 0.97).. Some urinary phytoestrogens were associated with cardiovascular and all-cause mortality in a representative sample of the US population. This is one of the first studies that used urinary phytoestrogens as biomarkers of their dietary intake to evaluate the effect of these bioactive compounds on the risk of death from cancer and cardiovascular disease.

    Topics: 4-Butyrolactone; Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Isoflavones; Lignans; Male; Middle Aged; Mortality; Neoplasms; Nutrition Surveys; Phytoestrogens; Proportional Hazards Models; Risk Factors; Treatment Outcome

2016
Anticancer activity studies of cubebin isolated from Piper cubeba and its synthetic derivatives.
    Bioorganic & medicinal chemistry letters, 2016, Apr-01, Volume: 26, Issue:7

    (-)-Cubebin, isolated from the seeds of Piper cubeba, and its five different types of derivatives (a total of 17), with varying functionalities, were tested for their in vitro anticancer activity against six human cancer cell lines (A549, K562, SiHa, KB, HCT116 and HT29) using MTT assay. Cubebin as well as its derivatives containing lactone and amide groups showed significant anticancer activity. In some of the tested cell lines, the amide derivatives showed higher activity. Morphological analysis indicated that these compounds act through apoptosis mediated pathway of cell death and we expect that these results will pave new paths in the development of novel anticancer agents by the derivatization of (-)-cubebin.

    Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Humans; Lignans; Models, Molecular; Neoplasms; Piper; Seeds

2016
Use of antibiotics is associated with lower enterolactone plasma concentration.
    Molecular nutrition & food research, 2016, Volume: 60, Issue:12

    High enterolactone levels may have health benefits in relation to risk of noncommunicable diseases. Enterolactone is produced by the colonic microbiota after intake of lignans and treatment with antimicrobials may result in altered enterolactone production. This study investigates the association between antibiotic use and enterolactone concentration.. Using LC-MS/MS, enterolactone concentrations were quantified in plasma samples from 2237 participants from the Diet, Cancer and Health cohort. The participants were healthy at enrollment, but were later diagnosed with cancer. At enrollment, participants had blood drawn and completed a food frequency questionnaire and lifestyle questionnaire. Antibiotic use was assessed as reimbursed antibiotic prescriptions up to 12 months before enrollment. Antibiotic use ≤3 months before enrollment was associated with a 41% (Δ. Use of antibiotics up to 12 months before enrollment was associated with lower plasma enterolactone levels, especially among women.

    Topics: 4-Butyrolactone; Anti-Bacterial Agents; Body Mass Index; Cohort Studies; Exercise; Female; Gastrointestinal Microbiome; Humans; Life Style; Lignans; Linear Models; Male; Middle Aged; Neoplasms; Nutrition Assessment; Risk Factors; Surveys and Questionnaires; Tandem Mass Spectrometry; Time Factors

2016
The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: pharmacogenomic determination of genes associated with sensitivity or resistance.
    Phytomedicine : international journal of phytotherapy and phytopharmacology, 2014, Apr-15, Volume: 21, Issue:5

    (-)-Sesamin is a lignan present in sesam oil and a number of medicinal plants. It exerts various pharmacological effects, such as prevention of hyperlipidemia, hypertension, and carcinogenesis. Moreover, (-)-sesamin has chemopreventive and anticancer activity in vitro and in vivo. Multidrug resistance (MDR) of tumors leads to fatal treatment outcome in many patients and novel drugs able to kill multidrug-resistant cells are urgently needed. P-glycoprotein (MDR1/ABCB1) is the best known ATP-binding cassette (ABC) drug transporter mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. We found that the mRNA expressions of ABCB1 and ABCB5 were not related to the 50% inhibition concentrations (IC50) for (-)-sesamin in a panel of 55 cell lines of the National Cancer Institute, USA. Furthermore, (-)-sesamin inhibited ABCB1- or ABCB5-overexpressing cells with similar efficacy than their drug-sensitive parental counterparts. In addition to ABC transporter-mediated MDR, we attempted to identify other molecular determinants of (-)-sesamin resistance. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell panel. Twenty-three genes were identified, whose mRNA expression correlated with the IC50 values for (-)-sesamin. These genes code for proteins of different biological functions, i.e. ribosomal proteins, components of the mitochondrial respiratory chain, proteins involved in RNA metabolism, protein biosynthesis, or glucose and fatty acid metabolism. Subjecting this set of genes to cluster analysis showed that the cell lines were assembled in the resulting dendrogram according to their responsiveness to (-)-sesamin. In conclusion, (-)-sesamin is not involved in MDR mediated by ABCB1 or ABCB5 and may be valuable to bypass chemoresistance of refractory tumors. The microarray expression profile, which predicted sensitivity or resistance of tumor cells to (-)-sesamin consisted of genes, which do not belong to the classical resistance mechanisms to established anticancer drugs.

    Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cluster Analysis; Dioxoles; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Gene Expression Profiling; HEK293 Cells; Humans; Lignans; Neoplasms; Phytotherapy; Plant Extracts

2014
Honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis.
    PloS one, 2014, Volume: 9, Issue:2

    Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC50 ranging 3.35 ± 0.13 µg/ml to 2.77 ± 0.22 µg/ml), despite their significant differences in response to paclitaxel (IC50 ranging 1.66 ± 0.09 ng/ml to 6560.9 ± 439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells, which was associated with inhibition of EGFR-STAT3 signaling and downregulation of STAT3 target genes. Combined treatment with honokiol and paclitaxel synergistically augmented cytotoxicity in MDR KB cells, compared with treatment with either agent alone in vitro. Importantly, the combined treatment significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model. Tumor tissues from the combination group displayed a significant inhibition of Ki-67 expression and an increase in TUNEL-positive cells compared with the control group. These results suggest that targeting multidrug resistance using honokiol in combination with chemotherapy drugs may provide novel therapeutic opportunities.

    Topics: Antineoplastic Agents; Apoptosis; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; ErbB Receptors; Humans; Ki-67 Antigen; Lignans; Mitochondria; Neoplasms; Paclitaxel; Receptors, Death Domain; Signal Transduction; STAT3 Transcription Factor

2014
A synthetic manassantin a derivative inhibits hypoxia-inducible factor 1 and tumor growth.
    PloS one, 2014, Volume: 9, Issue:6

    The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers.

    Topics: Animals; Apoptosis; Cell Cycle Checkpoints; Cell Hypoxia; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Drug Resistance, Neoplasm; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lignans; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Paclitaxel; Transcription, Genetic; Xenograft Model Antitumor Assays

2014
Bioactive lignan constituents from the twigs of Lindera glauca.
    Chemical & pharmaceutical bulletin, 2014, Volume: 62, Issue:11

    A bioassay-guided fractionation and chemical investigation of the MeOH extract from the twigs of Lindera glauca (SIEB. et ZUCC.) BLUME resulted in the isolation and identification of six lignans (1-6) including three new lignan derivatives, named linderuca A (1), B (2), and C (3). The structures of the new compounds (1-3) were determined on the basis of spectroscopic analyses, including two dimensional NMR and circular dichroism (CD) spectroscopy studies. The cytotoxic activities of the isolates (1-6) were evaluated by determining their inhibitory effects on human tumor cell lines. Compounds 1-5 showed antiproliferative activities against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC50 values of 7.79-29.42 µM. Based on the understanding that inflammation is a crucial cause of tumor progression, we also investigated the anti-inflammatory activities of the isolates (1-6) in the lipopolysaccharide-stimulated murine microglia BV-2 cell line by measuring nitric oxide (NO) levels. The new lignans (1-3) significantly inhibited NO production with IC50 values of 12.10, 9.48, and 9.87 µM, respectively, without cytotoxicity.

    Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Cell Line; Cell Line, Tumor; Cell Proliferation; Humans; Lignans; Lindera; Mice; Microglia; Neoplasms; Nitric Oxide; Plant Extracts

2014
Simonols A and B, two novel sesqui-neolignans from the fruits of Illicium simonsii.
    Fitoterapia, 2013, Volume: 88

    Two new sesqui-neolignans with novel conjugation way, simonol A (1), featuring a unique motif of a 5,5-dihydro-pyran with a hemiketal carbon, while simonol B (2) possessing two dihydronfuran rings in the same direction, were isolated from the ethanol extract of the fruits of Illicium simonii. Their structures were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and calculation of electronic circular dichroism (ECD) using density functional theory (DFT). The two isolates were evaluated for their inhibitory activities against the growth of four lines of human cancer cells (NCI-H460, SMMC-7721, MCF-7, BGC-823): 1 showed strong activities comparable to 5-Fluorouracil, and 2 to a less content. In addition, plausible biosynthetic routes for the two compounds were also proposed.

    Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Circular Dichroism; Fruit; Humans; Illicium; Lignans; Molecular Structure; Neoplasms; Phytotherapy; Plant Extracts

2013
Inducing apoptosis of cancer cells using small-molecule plant compounds that bind to GRP78.
    British journal of cancer, 2013, Jul-23, Volume: 109, Issue:2

    Glucose regulated protein 78 (GRP78) functions as a sensor of endoplasmic reticulum (ER) stress. The aim of this study was to test the hypothesis that molecules that bind to GRP78 induce the unfolded protein response (UPR) and enhance cell death in combination with ER stress inducers.. Differential scanning calorimetry (DSC), measurement of cell death by flow cytometry and the induction of ER stress markers using western blotting.. Epigallocatechin gallate (EGCG), a flavonoid component of Green Tea Camellia sinensis, and honokiol (HNK), a Magnolia grandiflora derivative, bind to unfolded conformations of the GRP78 ATPase domain. Epigallocatechin gallate and HNK induced death in six neuroectodermal tumour cell lines tested. Levels of death to HNK were twice that for EGCG; half-maximal effective doses were similar but EGCG sensitivity varied more widely between cell types. Honokiol induced ER stress and UPR as predicted from its ability to interact with GRP78, but EGCG was less effective. With respect to cell death, HNK had synergistic effects on melanoma and glioblastoma cells with the ER stress inducers fenretinide or bortezomib, but only additive (fenretinide) or inhibitory (bortezomib) effects on neuroblastoma cells.. Honokiol induces apoptosis due to ER stress from an interaction with GRP78. The data are consistent with DSC results that suggest that HNK binds to GRP78 more effectively than EGCG. Therefore, HNK may warrant development as an antitumour drug.

    Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Catechin; Cell Line, Tumor; Cell Survival; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Heat-Shock Proteins; Humans; Lignans; Molecular Targeted Therapy; Molecular Weight; Neoplasms; Protein Binding

2013
Dietary flavonoid and lignan intake and mortality in a Spanish cohort.
    Epidemiology (Cambridge, Mass.), 2013, Volume: 24, Issue:5

    Dietary flavonoids and lignans may protect against several chronic diseases, but there is little evidence on the relationship between flavonoid and lignan intake and mortality. We investigated the association between both all-cause and specific-cause mortality and intake of flavonoids and lignans in the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC-Spain) cohort.. The EPIC-Spain study follows 40,622 participants (38% men) aged 29-69 years. A validated diet history questionnaire was administered at recruitment. A food composition database was compiled based on US Department of Agriculture and Phenol-Explorer databases. Cox proportional hazards models, adjusted for confounders, were used in the analyses.. During a mean follow-up of 13.6 years, 1915 deaths were reported, with 416 from cardiovascular diseases (CVDs) and 956 from cancer. After adjustment for several potential confounders, the hazard ratios (HRs) for the highest versus the lowest quintile of dietary flavanone and flavonol intakes were 0.60 (95% confidence interval = 0.38-0.94) and 0.59 (0.40-0.88). Total flavonoid intake was also associated with a decrease in all-cause mortality (0.71 [0.49-1.03]). Lignan intake was not associated with all-cause mortality. In cause-specific mortality analyses, using competing risk regressions, doubling total flavonoid intake was inversely related to mortality from CVD (HR for log2 0.87 [0.77-0.98]), but not to mortality from either cancer (HR for log2 0.96 [0.89-1.04]) or other causes (HR for log2 0.97 [0.87-1.09]).. A diet high in flavonoids, particularly in flavanones and flavonols, is associated with a reduction in all-cause mortality, mainly of mortality from CVD.

    Topics: Adult; Aged; Cardiovascular Diseases; Cause of Death; Diet; Flavonoids; Follow-Up Studies; Humans; Lignans; Middle Aged; Neoplasms; Risk Factors; Spain

2013
Cytotoxic and potential anticancer constituents from the stems of Schisandra pubescens.
    Pharmaceutical biology, 2013, Volume: 51, Issue:9

    The diethyl ether extract of the stems of Schisandra pubescens Hemsl. et Wils. (Schisandraceae) was found to exhibit cytotoxic activity in vitro. However, investigations of the bioactive constituents of this plant have been very limited.. Elucidation of the cytotoxic constituents of S. pubescens was performed.. Repeated silica gel column chromatography and preparative TLC were used for the chemical investigation of the diethyl ether extract of S. pubescens stems. All isolates were evaluated for their in vitro cytotoxicity against A549, PC-3, KB and KBvin human cancer cell lines.. Nine known compounds were obtained, including four lignans, epischisandrone (1), tigloylgomisin P (2), cagayanone (3) and (-)-gomisin L₂ (4), together with five triterpenoids, micranoic acid B (5), lancifodilactone H (6), coccinic acid (7), schisanlactone B (8) and anwuweizonic acid (9). Compounds 2-6 and 8 showed moderate to marginal cytotoxicity, with GI₅₀ values of 11.83-35.65 μM.. The isolation of 1-9 from S. pubescens and the cytotoxicities of 3-6 are first reported. Compounds 2-6 and 8 could be the active principles responsible for the anticancer effects of S. pubescens.

    Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Drugs, Chinese Herbal; Ether; Ethnopharmacology; Humans; Inhibitory Concentration 50; Lignans; Neoplasms; Plant Extracts; Plant Stems; Schisandra; Solvents; Triterpenes; Tubulin Modulators; Vincristine

2013
Structure-cytotoxic activity relationship of sesquilignan, morinol A.
    Bioorganic & medicinal chemistry letters, 2013, Sep-01, Volume: 23, Issue:17

    The cytotoxic activities of sesquilignans, (7S,8S,7'R,8'R)- and (7R,8R,7'S,8'S)-morinol A and (7S,8S,7'S,8'S)- and (7R,8R,7'R,8'R)-morinol B were compared, showing no significant difference between stereoisomers (IC50=24-35 μM). As a next stage, the effect of substituents at 7, 7', and 7"-aromatic ring on the activity was evaluated to find out the higher activity of (7S,8S,7'R,8'R)-7,7',7"-phenyl derivative 18 (IC50=6-7 μM). In the research on the structure-activity relationship of 7"-position of (7S,8S,7'R,8'R)-7,7',7"-phenyl derivative 18, the most potent compounds were 7,7',7"-phenyl derivative 18 (IC50=6 μM) against HeLa cells. Against HL-60 cells, 7"-(4-nitrophenyl)-7,7'-phenyl derivative 33 and 7"-hexyl-7,7'-phenyl derivative 37 (IC50=5 μM) showed highest activity. We discovered the compounds showed four to sevenfold potent activity than that of natural (7S,8S,7'R,8'R)-morinol A. It was also confirmed that the 7'-benzylic hydroxy group have an important role for exhibiting activity, on the other hand, the resonance system of cinnamyl structure is not crucial for the potent activity.

    Topics: Antineoplastic Agents, Phytogenic; Cell Survival; Drugs, Chinese Herbal; HeLa Cells; HL-60 Cells; Humans; Lignans; Neoplasms; Pyrans; Structure-Activity Relationship

2013
Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun N-terminal kinase pathway.
    Anti-cancer drugs, 2013, Volume: 24, Issue:9

    Previous studies have reported that vitexins induce cytotoxic effects. In the present study, we investigate a new native lignan vitexin 6 (VB6) in vitro to determine the molecular mechanism underlying its cytotoxicity. We screened and cultured several tumor cell lines and subsequently analyzed VB6 cytotoxicity against 14 different tumor cell lines using a 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The expression of proteins that regulate apoptosis and autophagy was determined using western blot analysis. VB6 showed an excellent cytotoxic effect against various cancer cell lines in vitro. It induced apoptosis and autophagy of cancer cells. VB6-induced apoptosis showed a time-dependent and concentration-dependent relationship with cleaved poly (ADP-ribose) polymerase, cleaved caspase-3, Bax upregulation, and Bcl-2 downregulation. The levels of Beclin-1 and LC3-II, which are markers for cell autophagy, gradually increased after VB6 treatment. Jun N-terminal kinase (JNK) phosphorylation was increased after VB6 treatment, accompanied by upregulation of P-Bcl-2 and P-C-Jun expression. Cotreatment with a JNK inhibitor significantly decreased VB6-induced cell death and downregulated P-Bcl-2, and cleaved PARP and Beclin-1 expression. The new native lignan VB6 inhibits cancer cell proliferation by activating the JNK pathway. We believe that VB6 could be a valuable chemotherapeutic drug after further evaluation.

    Topics: Antineoplastic Agents, Phytogenic; Apigenin; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drugs, Chinese Herbal; Ethnopharmacology; Humans; Inhibitory Concentration 50; JNK Mitogen-Activated Protein Kinases; Kinetics; Lignans; MAP Kinase Signaling System; Neoplasm Proteins; Neoplasms; Protein Kinase Inhibitors; Seeds; Vitex

2013
8-9' linked neolignans with cytotoxicity from Alpinia conchigera.
    Fitoterapia, 2013, Volume: 91

    Five new 8-9' linked neolignans conchigeranals A-E (1-5), together with three known compounds galanganal (6), galanganols A (7) and B (8), were isolated from the whole plant of Alpinia conchigera. Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Cytotoxicities of compounds 1-8 were tested against two cancer cell lines A549 and Hela. Results showed that 4, 5, 7 and 8 exhibited cytotoxicity against A549 with the IC50 values of 12.36, 9.72, 10.26, 13.05 μg/ml, respectively, and 1-8 against Hela with the IC50 values from 1.53 to 5.29 μg/ml.

    Topics: Alpinia; Antineoplastic Agents, Phytogenic; Humans; Inhibitory Concentration 50; Lignans; Molecular Structure; Neoplasms; Phytotherapy; Plant Extracts

2013
Cytotoxic and antioxidant dihydrobenzofuran neolignans from the seeds of Crataegus pinnatifida.
    Fitoterapia, 2013, Volume: 91

    Eight new dihydrobenzofuran neolignans, pinnatifidanin C I-VIII (1-8), together with two known analogs (9-10) were isolated from the seeds of Crataegus pinnatifida. Their structures were elucidated by spectroscopic analyses, especially 1D, 2D NMR and CD spectra. The cytotoxic activities of all isolates against human cancer cell lines were assayed, and most interestingly, compound 10 revealed preferred cytotoxicity on the HT-1080 cell line and displayed much stronger inhibitory activity (IC50=8.86 μM) compared with positive control 5-fluorouracil (IC50=35.62 μM). Meanwhile, antioxidant activities of all the isolates were evaluated using 2,2-diphenyl-1-pikrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays, and the results showed that most of the isolates exhibited potent antioxidant activity.

    Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Benzofurans; Benzothiazoles; Biphenyl Compounds; Cell Line, Tumor; Crataegus; Humans; Inhibitory Concentration 50; Lignans; Molecular Structure; Neoplasms; Phytotherapy; Picrates; Plant Extracts; Seeds; Sulfonic Acids

2013
Dietary intake and major sources of plant lignans in Latvian men and women.
    International journal of food sciences and nutrition, 2013, Volume: 64, Issue:5

    Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40-75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169-5759) μg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).

    Topics: Adult; Aged; Bread; Butylene Glycols; Cardiovascular Diseases; Diet; Feeding Behavior; Female; Flax; Furans; Humans; Latvia; Lignans; Male; Middle Aged; Neoplasms; Phenols; Phytoestrogens; Plant Extracts; Sex Factors

2013
New antitumor compounds from Carya cathayensis.
    Bioorganic & medicinal chemistry letters, 2012, Mar-01, Volume: 22, Issue:5

    A new lignan (7R,8S,8'R)-4,4',9-trihydroxy-7,9'-epoxy-8,8'-lignan, and three new phenolics, carayensin-A, carayensin-B, and carayensin-C, together with 13 known compounds were isolated from the shells of Carya cathayensis. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. All the compounds were evaluated for cytotoxicity against several human tumor types including human colorectal cancer cell lines (HCT-116, HT-29), human lung cancer cell line (A549), and human breast cancer cell line (MCF-7). The compounds 1, 5, 6, and 16 are considered to be potential as antitumor agents, which could significantly inhibit the cancer cell growth in a dose-dependent manner.

    Topics: Antineoplastic Agents, Phytogenic; Carya; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Humans; Lignans; Magnetic Resonance Spectroscopy; Neoplasms; Plant Extracts

2012
Two New Norlignans and a New Lignanamide from Peperomia tetraphylla.
    Chemistry & biodiversity, 2012, Volume: 9, Issue:4

    Two new cyclobutane-type norlignans, methyl rel-(1R,2S,3S)-2-(7-methoxy-1,3-benzodioxol-5-yl)-3-(2,4,5-trimethoxyphenyl)cyclobutanecarboxylate (1), and methyl rel-(1R,2R,3S)-2-(7-methoxy-1,3-benzodioxol-5-yl)-3-(2,4,5-trimethoxyphenyl)cyclobutanecarboxylate (2), and a new lignanamide, 3-hydroxy-N-[2-(4-hydroxyphenyl)ethyl]-α-[4-(2-{N-[2-(4-hydroxyphenyl)ethyl]carbamoyl}ethenyl)-3-methoxyphenoxy]-4-methoxycinnamamide 4,8″-ether (3), along with five known amides, 4-8, were obtained from the whole plant of Peperomia tetraphylla. Their structures were elucidated mainly by the analysis of NMR and MS data. The new compounds 1-3 and the known compound 4 were tested for their cytotoxic activities against the HepG2 (human hepatocarcinoma), A549 (human lung cancer), and HeLa (human cervical cancer) cell lines. Compound 4 showed significant cytotoxicity against HepG2 cell lines with an IC(50) value of 9.4 ± 1.0 μM.

    Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Survival; Cyclobutanes; Drug Screening Assays, Antitumor; HeLa Cells; Hep G2 Cells; Humans; Lignans; Neoplasms; Peperomia

2012
Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort.
    European journal of clinical nutrition, 2012, Volume: 66, Issue:8

    Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.. Single 24-hour dietary recalls were collected from 36,037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres.. Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages.. There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

    Topics: Adult; Aged; Beverages; Body Mass Index; Cardiovascular Diseases; Coumarins; Diet; Edible Grain; Energy Intake; Equol; Europe; Female; Fruit; Glycine max; Humans; Isoflavones; Life Style; Lignans; Male; Middle Aged; Neoplasms; Nutritional Status; Phytoestrogens; Prospective Studies; Vegetables

2012
Cytotoxic sesquiterpenes and lignans from Saussurea deltoidea.
    Fitoterapia, 2012, Volume: 83, Issue:6

    Two new sesquiterpenes deltoiden A (1) and deltoiden B (2), and two new lignans deltoignan A (9) and deltoignan B (10), together with 14 known compounds, including six sesquiterpenes 3-8 and three lignans 11-13, were isolated from the whole plant of Saussurea deltoidea. Compounds 3-8 and 11-17 were isolated for the first time from this plant. Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Cytotoxicities of compounds 1-13 were tested against three cancer cell lines A549, Hela and SMMC-7721. Results showed that 5, 6 and 7 exhibited cytotoxicity against SMMC-7721 with the IC(50) values of 6.49, 9.53, 1.23 μg/ml, 5 and 7 against A549 with the IC(50) values of 4.99 and 5.35 μg/ml, 5, 6, 7, 13 against Hela with the IC(50) values of 1.40, 4.75, 0.93 and 5.42 μg/ml, respectively. The structure-activity relationships of sesquiterpenes 1-8 were discussed on the base of cytotoxic results.

    Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; HeLa Cells; Humans; Inhibitory Concentration 50; Lignans; Molecular Structure; Neoplasms; Phytotherapy; Plant Extracts; Saussurea; Sesquiterpenes; Structure-Activity Relationship

2012
Lignans and triterpenes from the root of Pseuderanthemum carruthersii var. atropurpureum.
    Chemical & pharmaceutical bulletin, 2012, Volume: 60, Issue:9

    Two new lignans, pseuderesinol (1), pseuderanoside (2) and a new triterpene, pseuderanic acid (3) were isolated from the dried root of Pseuderanthemum carruthersii (SEEM.) GUILL. var. atropurpureum (BULL.) FOSB. (Acanthaceae), together with ten known compounds, including five lignans, (+)-eudesmin (4), (+)-magnolin (5), (+)-syringaresinol (6), (+)-episyringaresinol (7), (+)-1-hydroxysyringaresinol (8) and five triterpenes, squalene (9), oleanolic acid (10), lupeol (11), betulin (12), betulinic acid (13). Their chemical structures were elucidated by 1D- and 2D-NMR, computational quantum chemistry, as well as high resolution-electrospray ionization (HR-ESI)-MS spectroscopic analysis. The acetylcholinesterase inhibition and cytotoxic activities against HeLa and MCF-7 cancer cell lines were evaluated on some purified compounds at the concentration of 100 µg/mL. Pseuderesinol (1) and magnolin (5) exhibited moderate cytotoxic activities against the MCF-7 cancer cell line.

    Topics: Acanthaceae; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Survival; Humans; Lignans; Neoplasms; Plant Roots; Triterpenes

2012
[Identification of two small molecule inhibitors of hypoxia-inducible factor 1 with different cell-based screening model].
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2012, Volume: 37, Issue:14

    To investigate the inhibitory activity of HIF-1 by triptolide and manasaantin A, two cell-based models with luciferase report gene assay were established.. Two cell-based models of HIF-1 were used to evaluate HIF-1 inhibition activity of triptolide and manasaantin A. Secreted VEGF expression induced by hypoxia was detected by ELISA with two compounds. The growth inhibition of different solid tumor cell lines was measured by the MTT assay.. The expression of firefly luciferase was induced by hypoxia in U251-HRE and T47D-HRE cells. U251-HRE model was suitable for the detection of HIF-1 inhibition activity of triptolide. The IC50 of triptolide on HIF-1 activity was (3.4 +/- 0.5) x 10(-8) mol x L(-1). The report gene assay using T47D cells co-transfected with pGL2-TK-HRE and pRL-CMV showed more sensitive inhibition activity of HIF-1 on manassantin A than that of detected by U251-HRE model. The IC50 of manassantin A on HIF-1 activity was (2.4 +/- 0.6) x 10(-8) mol x L(-1). HIF-1 target gene VEGF was also inhibited by test compounds on protein level in T47D cells. Manasaantin A showed selective inhibition on the growth of human solid cancer cell lines, especially on breast cancer and pancreatic cancer cells. Meanwhile, triplotide showed strong proliferation inhibition activity on all tested cell lines.. It is very important to select a suitable cell-based report gene assay of HIF-1 for screening of different kinds of inhibitor.

    Topics: Cell Line, Tumor; Cell Proliferation; Diterpenes; Drug Evaluation, Preclinical; Epoxy Compounds; Humans; Hypoxia-Inducible Factor 1; Lignans; Luciferases; Models, Biological; Neoplasms; Phenanthrenes

2012
Honokiol inhibits hypoxia-inducible factor-1 pathway.
    International journal of radiation biology, 2011, Volume: 87, Issue:6

    Hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in the reaction of a tumour to hypoxia. In this study, we examined the inhibitory effect of a natural compound, honokiol, on HIF-1α activity and tumour growth in combination with radiation.. The inhibitory effect of honokiol on hypoxia-responsive element (HRE) controlled luciferase activity and HIF-1α accumulations stimulated by CoCl(2), or hypoxia was examined. Effect of honokiol on HIF-1α levels within hypoxic tumour microenvironment was investigated by immunohistochemical and in vivo bioluminescent studies. The in vivo radiosensitising activity of honokiol was evaluated with subcutaneous murine colon carcinoma, CT26, xenografts of BALB/c mice treated with honokiol, radiation, or both.. Suppression of luciferase (luc) activity in HRE-luc stable cells by honokiol was in agreement with the results of decreased HIF-1α accumulation. In CT26-HRE-luc tumour-bearing mice, the inhibitory effect of intraperitoneally injected honokiol on HIF-1α-regulated luciferase activities induced by either CoCl(2) or radiation could be monitored non-invasively. Lastly, honokiol in combination with irradiation produced synergistic delay of CT26 tumour growth.. Our data suggest that honokiol can exert its anticancer activity as a HIF-1α inhibitor by reducing HIF-1α protein level and suppressing the hypoxia-related signaling pathway. The animal experiment indicates that honokiol improves the therapeutic efficacy of radiation.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cobalt; Enzyme-Linked Immunosorbent Assay; Female; HeLa Cells; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Immunohistochemistry; Lignans; Luciferases; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Neoplasms

2011
Metabolic and pharmacokinetic studies of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor after intragastric administration of nanoparticle formulations by liquid chromatography coupled with tandem mass spectrometry.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2011, Sep-15, Volume: 879, Issue:26

    This paper aims to investigate the metabolism and pharmacokinetics of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor. To improve water solubility, nanoparticle formulations were prepared as curcuminoids-loaded solid lipid nanoparticles (curcuminoids-SLNs) and curcumin-loaded solid lipid nanoparticles (curcumin-SLNs). After intragastric administration to tumor-bearing ICR mice, the plasma and tumor samples were analyzed by liquid chromatography with ion trap mass spectrometry. We discovered that curcuminoids were mainly present as glucuronides in plasma, whereas in free form in tumor tissue. A validated LC/MS/MS method was established to determine the three free curcuminoids in tumor homogenate. Samples were separated on a Zorbax SB-C(18) column, eluted with acetonitrile-water (containing 0.1% formic acid), and detected by TSQ Quantum triple quadrupole mass spectrometer in selected reaction monitoring mode. The method showed good linearity (r(2)=0.997-0.999) over wide dynamic ranges (2-6000 ng/mL). Variations within- and between-batch never exceeded 11.2% and 13.4%, respectively. The extraction recovery rates ranged from 78.3% to 87.7%. The pharmacokinetics of curcuminoids in mice tumor fit two-compartment model and first order elimination. For curcumin-SLNs group, the dosing of 250 mg/kg of curcumin resulted in AUC((0-48 h)) of 2285 ngh/mL and C(max) of 209 ng/mL. For curcuminoids-SLNs group, the dosing equivalent to 138 mg/kg of curcumin resulted in higher tumor concentrations (AUC=2811 ngh/mL, C(max)=285 ng/mL). It appeared that co-existing curcuminoids improved the bioavailability of curcumin.

    Topics: Animals; Area Under Curve; Biphenyl Compounds; Chromatography, Liquid; Curcumin; Diarylheptanoids; Drug Delivery Systems; Drug Stability; Lignans; Linear Models; Lipids; Male; Mice; Mice, Inbred ICR; Nanoparticles; Neoplasm Transplantation; Neoplasms; Reproducibility of Results; Tandem Mass Spectrometry

2011
Anti-angiogenic and cytotoxicity studies of some medicinal plants.
    Planta medica, 2010, Volume: 76, Issue:9

    Angiogenesis plays an important role in tumor formation and proliferation. The development of anti-angiogenic agents to block new blood vessel growth will inhibit metastasis and induce apoptosis of the cancer cells. Nine medicinal plants, Strobilanthes crispus, Phyllanthus niruri, Phyllanthus pulcher, Phyllanthus urinaria, Ailanthus malabarica, Irvingia malayana, Smilax myosotiflora, Tinospora crispa and blumea balsamifera were screened for anti-angiogenic properties using the rat aortic ring assay. Of these, the methanol extracts of Phyllanthus species and Irvingia malayana exhibited the highest activity. At 100 microg/mL, P. pulcher, P. niruri, P. urinaria and I. malayana recorded an inhibition of 78.8 %, 59.5 %, 56.7 % and 46.4 %, respectively, against rat aortic vascular growth. Their activities were further investigated by the tube formation assay involving human umbilical vein endothelial cells (HUVEC) on Matrigel. I. malayana, P. niruri and P. urinaria showed a significant decrease of 45.5, 37.9 and 35.6 %, respectively, whilst P. pulcher showed a much lower decrease of 15.5 % when compared with that of the rat aortic ring assay. All the plant extracts were evaluated for cytotoxicity on a panel of human cancer cell lines using the MTT assay. None of them displayed acute cytotoxicity. The HPLC of P. niruri, P. urinaria and P. pulcher indicated the extracts contained some identical chromatographic peaks of lignans. Further fractionation of I. malayana yielded betulinic acid reported in this plant for the first time and at 100 microg/mL it exhibited a 67.3 % inhibition of vessel outgrowth and 46.5 % inhibition of tube formation.

    Topics: Angiogenesis Inhibitors; Animals; Aorta; Betulinic Acid; Cell Line, Tumor; Endothelial Cells; Humans; Lignans; Neoplasms; Pentacyclic Triterpenes; Plant Extracts; Plants, Medicinal; Rats; Triterpenes; Umbilical Veins

2010
Phenolic compounds as selective antineoplasic agents against multidrug-resistant human cancer cells.
    Planta medica, 2010, Volume: 76, Issue:10

    Twelve phenolic compounds, including three stilbenes, two flavonoids, two coumarins, one neolignan, and four lignans, isolated from Euphorbia and Pycnanthus species or obtained by derivatization, were assayed for their potential antineoplastic efficacy in three human cancer cell lines: gastric (EPG85-257), pancreatic (EPP85-181), and colon (HT-29) carcinomas as well as derived multidrug-resistant sublines. In each case, two different multidrug-resistant variants, i.e., cell lines with classical and atypical MDR phenotype, were used. The majority of the MDR cancer sublines showed increased sensitivities to the studied compounds when compared to the parental sublines. The most active compound was the flavonoid naringenin, found to be 15-fold more effective against the atypical MDR subline of gastric carcinoma than in parental drug-sensitive cells. Furthermore, the stilbene trans-3,5,3',4'-tetramethoxypiceatannol and the lignans 4'-hydroxy-3,3',4-trimethoxylignan and heliobuphthalmin also exhibited high antineoplasic activities against the classical MDR subline derived from gastric carcinoma. The results of this study suggest that some phenolic compounds might be valuable for the treatment of multidrug-resistant cancer cells.

    Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Colonic Neoplasms; Drug Resistance, Multiple; Euphorbia; Flavanones; Humans; Lignans; Magnoliopsida; Myristicaceae; Neoplasms; Pancreatic Neoplasms; Phenols; Phytotherapy; Plant Extracts; Stilbenes; Stomach Neoplasms

2010
Lignans from Santalum album and their cytotoxic activities.
    Chemical & pharmaceutical bulletin, 2010, Volume: 58, Issue:4

    A new neolignan, (7R,8R)-5-O-demethylbilagrewin (1), together with four known lignans (2-5), were isolated from the heartwood of Santalum album (Santalaceae). The structure of 1 was determined by analysis of extensive spectroscopic data. The isolated compounds and derivatives were evaluated for their cytotoxic activities against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells. Compounds 1 and 2 exhibited cytotoxicity against HL-60 cells with IC(50) values of 1.5+/-0.02 and 4.3+/-0.13 microM, and against A549 cells with IC(50) values of 13.6+/-0.32 and 19.9+/-1.27 microM, respectively. The aldehyde group of 1 and 2 was revealed to be a structural requirement for the appearance of cytotoxicity in this type of lignans. These tumor cell deaths were shown to be mediated through induction of apoptosis.

    Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cytotoxins; DNA Fragmentation; Humans; Leukemia; Lignans; Lung Neoplasms; Molecular Structure; Neoplasms; Santalum

2010
Sesamin manifests chemopreventive effects through the suppression of NF-kappa B-regulated cell survival, proliferation, invasion, and angiogenic gene products.
    Molecular cancer research : MCR, 2010, Volume: 8, Issue:5

    Agents that are safe, affordable, and efficacious are urgently needed for the prevention of chronic diseases such as cancer. Sesamin, a lipid-soluble lignan, is one such agent that belongs to a class of phytoestrogens, isolated from sesame (Sesamum indicum), and has been linked with prevention of hyperlipidemia, hypertension, and carcinogenesis through an unknown mechanism. Because the transcription factor NF-kappaB has been associated with inflammation, carcinogenesis, tumor cell survival, proliferation, invasion, and angiogenesis of cancer, we postulated that sesamin might mediate its effect through the modulation of the NF-kappaB pathway. We found that sesamin inhibited the proliferation of a wide variety of tumor cells including leukemia, multiple myeloma, and cancers of the colon, prostate, breast, pancreas, and lung. Sesamin also potentiated tumor necrosis factor-alpha-induced apoptosis and this correlated with the suppression of gene products linked to cell survival (e.g., Bcl-2 and survivin), proliferation (e.g., cyclin D1), inflammation (e.g., cyclooxygenase-2), invasion (e.g., matrix metalloproteinase-9, intercellular adhesion molecule 1), and angiogenesis (e.g., vascular endothelial growth factor). Sesamin downregulated constitutive and inducible NF-kappaB activation induced by various inflammatory stimuli and carcinogens, and inhibited the degradation of IkappaBalpha, the inhibitor of NF-kappaB, through the suppression of phosphorylation of IkappaBalpha and inhibition of activation of IkappaBalpha protein kinase, thus resulting in the suppression of p65 phosphorylation and nuclear translocation, and NF-kappaB-mediated reporter gene transcription. The inhibition of IkappaBalpha protein kinase activation was found to be mediated through the inhibition of TAK1 kinase. Overall, our results showed that sesamin may have potential against cancer and other chronic diseases through the suppression of a pathway linked to the NF-kappaB signaling.

    Topics: Angiogenic Proteins; Antineoplastic Agents; Antioxidants; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dioxoles; Growth Inhibitors; Humans; Lignans; Neoplasm Invasiveness; Neoplasms; Neovascularization, Pathologic; NF-kappa B; Sesame Oil; Signal Transduction

2010
Antineoplastic effects of Magnoliae officinalis in tumours other than hepatomas.
    Liver international : official journal of the International Association for the Study of the Liver, 2009, Volume: 29, Issue:6

    Topics: Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Humans; Lignans; Magnolia; Neoplasms; Plant Extracts

2009
Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2009, Aug-15, Volume: 15, Issue:16

    Lignans such as secoisolariciresinol diglucoside in flaxseed, are metabolizes to bioactive mammalian lignans of END and ENL. Because mammalian lignans have chemical structural similarity to the natural estrogen, they are thought to behave like selective estrogen receptor modulators and therefore have anticancer effect against hormone-related cancers. We isolated a series of lignan compounds, named as Vitexins, from the seed of Chinese herb Vitex Negundo.. We purified several Vitexin lignan compounds. Cytotoxic and antitumor effects were analyzed in cancer cells and in tumor xenograft models. In vivo metabolism of Vitexins was determined in rat.. Contrasts to the classic lignans, Vitexins were not metabolized to END and ENL. A mixture of Vitexins EVn-50 and purified Vitexin compound 6-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-3, 4-dihydro-2-naphthaldehyde have cytotoxic effect on breast, prostate, and ovarian cancer cells and induces apoptosis with cleavage in poly ADP ribose polymerase protein, up-regulation of Bax, and down-regulation of Bcl-2. This induction of apoptosis seems to be mediated by activation of caspases because inhibition of caspases activity significantly reduced induced apoptosis. We showed a broad antitumor activity of EVn-50 on seven tumor xenograft models including breast, prostate, liver, and cervical cancers. Consistent with in vitro data, EVn-50 treatment induced apoptosis, down-regulated of Bcl-2, and up-regulated Bax in tumor xenografts.. Vitexin is a class of nature lignan compounds, whose action and anticancer effect is mediated by the mechanisms different from the classic lignans. Vitexin-induced antitumor effect and cytotoxic activity is exerted through proapoptotic process, which is mediated by a decreased Bcl-2/Bax ratio and activation of caspases.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Apigenin; Apoptosis; Cell Proliferation; Female; Flavonoids; HeLa Cells; Humans; Lignans; Male; Mice; Mice, Nude; Models, Biological; Neoplasms; Rats; Rats, Sprague-Dawley; Tumor Burden; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

2009
Honokiol suppresses survival signals mediated by Ras-dependent phospholipase D activity in human cancer cells.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2008, Jul-01, Volume: 14, Issue:13

    Elevated phospholipase D (PLD) activity provides a survival signal in several human cancer cell lines and suppresses apoptosis when cells are subjected to the stress of serum withdrawal. Thus, targeting PLD survival signals has potential to suppress survival in cancer cells that depend on PLD for survival. Honokiol is a compound that suppresses tumor growth in mouse models. The purpose of this study was to investigate the effect of honokiol on PLD survival signals and the Ras dependence of these signals.. The effect of honokiol upon PLD activity was examined in human cancer cell lines where PLD activity provides a survival signal. The dependence of PLD survival signals on Ras was investigated, as was the effect of honokiol on Ras activation.. We report here that honokiol suppresses PLD activity in human cancer cells where PLD has been shown to suppress apoptosis. PLD activity is commonly elevated in response to the stress of serum withdrawal, and, importantly, the stress-induced increase in PLD activity is selectively suppressed by honokiol. The stress-induced increase in PLD activity was accompanied by increased Ras activation, and the stress-induced increase in PLD activity in MDA-MB-231 breast cancer cells was dependent on a Ras. The PLD activity was also dependent on the GTPases RalA and ADP ribosylation factor. Importantly, honokiol suppressed Ras activation.. The data provided here indicate that honokiol may be a valuable therapeutic reagent for targeting a large number of human cancers that depend on Ras and PLD for their survival.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Cell Line, Tumor; Cell Survival; Enzyme Activation; Humans; Lignans; Mice; Models, Chemical; Neoplasm Transplantation; Neoplasms; Phospholipase D; ras Proteins; Signal Transduction

2008
Selection methodology with scoring system: application to Mexican plants producing podophyllotoxin related lignans.
    Journal of ethnopharmacology, 2008, Dec-08, Volume: 120, Issue:3

    As most anticancer drugs are derived from natural sources, the screening of local medicinal flora should be considered a primary step in the search for new sources for antineoplastic agents. In Mexico, more than 6000 medicinal plant species are used for the treatment of various diseases, including cancer. A multifactorial plant selection method, employing various criteria was designed and applied in order to select alternative sources of podophyllotoxin lignan analogues. For each criterion (chemotaxonomy, traditional medical uses and published scientific data), an arbitrary score system was ascribed to the species and the sum of these enabled us to compare potential candidates. The resulting selected plants were tested for cytotoxic activity and the compounds responsible for this activity were evaluated by liquid chromatography-mass spectroscopy (LC-MS). Around 50 species from the Mexican flora were initially considered. From these, six species were selected by referring to the results from the scoring system and these were then collected. Three extracts were evaluated as being highly cytotoxic against three different cancer cell lines. Finally, podophyllotoxin-like lignans could be identified by observing the fragmentation pattern on mass spectra, obtained from the LC-MS in two species: Linum scabrellum and Hyptis suaveolens.

    Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Humans; Lignans; Mexico; Neoplasms; Phytotherapy; Plant Extracts; Plants, Medicinal; Podophyllotoxin; Research Design

2008
Honokiol induces a necrotic cell death through the mitochondrial permeability transition pore.
    Cancer research, 2007, May-15, Volume: 67, Issue:10

    Previous reports have shown that honokiol induces apoptosis in numerous cancer cell lines and showed preclinical efficacies against apoptosis-resistant B-cell chronic lymphocytic leukemia and multiple myeloma cells from relapse-refractory patients. Here, we show that honokiol can induce a cell death distinct from apoptosis in HL60, MCF-7, and HEK293 cell lines. The death was characterized by a rapid loss of integrity of plasma membrane without externalization of phosphatidyl serine. The broad caspase inhibitor z-VAD-fmk failed to prevent this cell death. Consistently, caspase activation and DNA laddering were not observed. The death was paralleled by a rapid loss of mitochondrial membrane potential, which was mechanistically associated with the mitochondrial permeability transition pore regulated by cyclophilin D (CypD) based on the following evidence: (a) cyclosporin A, an inhibitor of CypD (an essential component of the mitochondrial permeability transition pore), effectively prevented honokiol-induced cell death and loss of mitochondrial membrane potential; (b) inhibition of CypD by RNA interference blocked honokiol-induced cell death; (c) CypD up-regulated by honokiol was correlated with the death rates in HL60, but not in K562 cells, which underwent apoptosis after being exposed to honokiol. We further showed that honokiol induced a CypD-regulated death in primary human acute myelogenous leukemia cells, overcame Bcl-2 and Bcl-X(L)-mediated apoptotic resistance, and was effective against HL60 cells in a pilot in vivo study. To the best of our knowledge, this is the first report to document an induction of mitochondrial permeability transition pore-associated cell death by honokiol.

    Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Apoptosis Inducing Factor; Biphenyl Compounds; Cell Death; Cell Line, Tumor; Cell Nucleus; Cyclophilins; Female; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; Lignans; Male; Membrane Potential, Mitochondrial; Middle Aged; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Necrosis; Neoplasms; Reactive Oxygen Species

2007
The chemopreventive effects of Saussurea salicifolia through induction of apoptosis and phase II detoxification enzyme.
    Biological & pharmaceutical bulletin, 2007, Volume: 30, Issue:12

    The ethanol extract of the aerial part of the Mongolian medicinal plant Saussurea salicifolia induced a dose-dependent cell growth inhibition in both human gastric adenocarcinoma AGS cells and mouse hepatoma Hepa 1c1c7 cells (IC(50)=30.22 and 116.96 mug/ml), respectively. The extract induced an apoptosis in AGS cells inference from the externalization of the phosphatidylserine, the increase of the sub G0/G1 content (%) and the apoptotic morphological changes including membrane blebbing, the formation of apoptotic bodies and chromatin condensation. In order to identify active substances causing the apoptosis, we further isolated major compounds present in Saussurea salicifolia and 7 compounds were isolated including a sesquiterpene lactone, cynaropicrin, 3 lignans (trachelogenin, matairesinol and arctigenin) and 3 lignan glycosides (tracheloside, matairesinoside and arctiin). In general the lignan aglycones were more cytotoxic than their lignan glycosides in both AGS cells and Hepa 1c1c7 cells. Cynaropicrin not only showed the most potent cytotoxicity among the 7 major compounds but also it induced an apoptosis and a weak G2/M arrest in AGS cells. Arctigenin had the second-best cytotoxicity among 7 major compounds, and induced an apoptosis. In order to evaluate the induction of the phase II detoxification enzyme, we measured the induction of quinone reductase activity of the extract, fractions and compounds in Hepa 1c1c7 cells. The ethyl acetate fraction and arctigenin showed the strongest cancer chemopreventive activity (chemoprevention index=9.88 and 7.57, respectively). These data suggest that the extract as well as the lignan compounds (especially arctigenin) originated from Saussurea salicifolia may be served as potential cancer chemopreventive agents for prevention or treatment of human cancers.

    Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Proliferation; Chromatin; DNA, Neoplasm; Enzyme Induction; Ethanol; Flow Cytometry; Furans; Humans; Lactones; Lignans; Metabolic Detoxication, Phase II; NAD(P)H Dehydrogenase (Quinone); Neoplasms; Plant Extracts; Saussurea; Sesquiterpenes; Solvents; Tetrazolium Salts; Thiazoles

2007
Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF-7 xenografts in ovariectomized athymic nude mice.
    International journal of cancer, 2006, Mar-01, Volume: 118, Issue:5

    This study determined the effect of the mammalian lignans enterolactone (ENL) and enterodiol (END) alone and in combination with the isoflavone genistein (GEN) on the growth of MCF-7 tumors in ovariectomized nude mice. Ovariectomized athymic nude mice with established MCF-7 tumors were fed a basal diet (AIN-93G) and divided into 5 groups that received daily subcutaneous injections (10 mg/kg body weight (BW)) of ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. A positive control group was implanted with an estradiol pellet in order to establish an estrogenic tumor growth response. In the ENL- and END-treated mice, palpable tumors regressed significantly by 91 and 83%, respectively, resulting in final tumors that were similar to the negative control tumors. However, tumor cell apoptosis was significantly enhanced by the lignans. In the GEN-treated mice, tumors initially regressed significantly by 64% but regression ceased following prolonged treatment, resulting in final tumors that were significantly larger compared to negative control, ENL-, and END-treated mice, in part by increasing tumor cell proliferation. The MIX treatment significantly regressed palpable tumors by 87% similar to negative control group, with no effects on tumor cell apoptosis or proliferation. The isoflavone GEN alone promoted the growth of established MCF-7 human breast cancer xenografts after prolonged treatment while the mammalian lignans ENL and END did not. When these phytoestrogens were given in combination, no tumor growth-promoting effects were observed. (c) 2005 Wiley-Liss, Inc.

    Topics: 4-Butyrolactone; Animals; Apoptosis; Body Weight; Cell Line, Tumor; Cell Proliferation; Drug Therapy, Combination; Feeding Behavior; Genistein; Humans; Lignans; Mice; Mice, Nude; Neoplasms; Ovariectomy; Xenograft Model Antitumor Assays

2006
Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the Zutphen Elderly Study.
    The American journal of clinical nutrition, 2006, Volume: 84, Issue:2

    Plant lignans are converted to enterolignans that have antioxidant and weak estrogen-like activities, and therefore they may lower cardiovascular disease and cancer risks.. We investigated whether the intakes of 4 plant lignans (lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol) were inversely associated with coronary heart disease (CHD), cardiovascular diseases (CVD), cancer, and all-cause mortality.. The Zutphen Elderly Study is a prospective cohort study in which 570 men aged 64-84 y were followed for 15 y. We recently developed a database and used it to estimate the dietary intakes of 4 plant lignans. Lignan intake was related to mortality with the use of Cox proportional hazards analysis.. The median total lignan intake in 1985 was 977 microg/d. Tea, vegetables, bread, coffee, fruit, and wine were the major sources of lignan. The total lignan intake was not related to mortality. However, the intake of matairesinol was inversely associated with CHD, CVD, and all-cause mortality (P

    Topics: Aged; Aged, 80 and over; Butylene Glycols; Cardiovascular Diseases; Cause of Death; Cohort Studies; Coronary Disease; Diet; Diet Surveys; Furans; Humans; Lignans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Netherlands; Proportional Hazards Models; Prospective Studies; Wine

2006
Schisandrin B--a novel inhibitor of P-glycoprotein.
    Biochemical and biophysical research communications, 2005, Sep-23, Volume: 335, Issue:2

    P-glycoprotein-mediated drug efflux is one of the major causes of the cancer multidrug resistance (MDR). Inhibition of P-glycoprotein could reverse cancer MDR. Here, we show that schisandrin B, a naturally occurring compound from Schisandra chinensis (Turcz.) Baill, bears strong potency to inhibit P-glycoprotein. Schisandrin B reversed the drug resistance of four MDR cell lines characterized with overexpression of P-glycoprotein and fully restored the intracellular drug accumulation by interacting with P-glycoprotein. Schisandrin B has a core structure of dibenzocyclooctadiene, representing a novel P-glycoprotein inhibitor. To our best knowledge, the role of schisandrin B to inhibit P-glycoprotein has not been reported.

    Topics: Affinity Labels; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Azides; Cell Line, Tumor; Cell Proliferation; Cyclooctanes; Daunorubicin; Dihydropyridines; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Humans; Inhibitory Concentration 50; K562 Cells; Lignans; Models, Chemical; Neoplasms; Polycyclic Compounds; Protein Binding; Tetrazolium Salts; Thiazoles; Time Factors

2005
[Selected phytoestrogens with potential beneficial effects on risk of certain environmental diseases].
    Casopis lekaru ceskych, 2000, Volume: 139 Suppl 1

    Evidence has been accumulated that some phytoestrogens act as protective factors against development of cancer and also cardiovascular diseases. These are phytoestrogens of isoflavone and lignane series, found especially in soy. Beneficial effect of these compounds may be explained by a complexity of their actions at various levels: they interact with estrogen receptors, some of them are inhibitors of the key enzymes responsible in the final effect for cell growth and proliferation, and, due to their chemical nature they are scavengers of free radicals. In the presented work the authors, in collaboration with Finnish partners from the University of Helsinki, developed original immunoassays for determination of main phytoestrogens of isoflavone series--daidzein, genistein, formononoetin, biochanin A, their metabolite equal and lignane enterolactone. The methods are sensitive enough for follow-up of actual levels of phytoestrogens in serum. By using these methods, the levels of phytoestrogens in Czech population have been established. The group of patients suffering from osteoporosis has been investigated, too. Significantly lower levels of isoflavonoids in comparison with sex- and age-matched healthy subject have been found in the patients. The methods have also enabled us to follow up the dynamics of these compounds in the organism, as well as to determine their content in food and its sources. The original detection and quantification of four above mentioned isoflavonoids in beer is an example.

    Topics: Anticarcinogenic Agents; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Lignans; Neoplasms; Osteoporosis, Postmenopausal; Plants; Radioimmunoassay

2000
Phytoestrogens. Friends or foes?
    Environmental health perspectives, 1996, Volume: 104, Issue:5

    Topics: Animals; Diet; Female; Glycine max; Humans; In Vitro Techniques; Isoflavones; Lignans; Menopause; Neoplasms; Osteoporosis; Plant Growth Regulators; Plants, Edible

1996
Determination of lignans and isoflavonoids in human female plasma following dietary supplementation.
    The Journal of endocrinology, 1994, Volume: 142, Issue:2

    Plasma levels of the lignans enterodiol and enterolactone, and also the isoflavonic phyto-oestrogens daidzein, equol and genistein, are reported for postmenopausal Australian women consuming a traditional diet supplemented with linseed, soya flour or clover sprouts. Analysis was performed by gas chromatography-mass spectrometry, after enzymatic hydrolysis and ion-exchange chromatography. Following linseed supplementation, combined levels of enterolactone and enterodiol reached 500 ng/ml, whereas after soya flour or clover sprouts the respective concentrations of equol, daidzein and genistein reached 43, 312 and 148 ng/ml. Not all subjects were able to produce equol from daidzein. The possible relationship and role of these weak dietary oestrogens as restraining factors in the development of hormone-dependent cancers in Asian populations is discussed.

    Topics: 4-Butyrolactone; Australia; Chromans; Diet; Equol; Estrogens; Female; Food, Fortified; Gas Chromatography-Mass Spectrometry; Genistein; Glycine max; Humans; Isoflavones; Lignans; Linseed Oil; Middle Aged; Monoamine Oxidase Inhibitors; Neoplasms; Plants, Edible; Postmenopause

1994
Lignans--additional benefits from fiber?
    Nutrition and cancer, 1984, Volume: 6, Issue:2

    Topics: Animals; Dietary Fiber; Female; Humans; Lignans; Male; Neoplasms; Plant Extracts; Plants; Risk

1984
Lignan formation in man--microbial involvement and possible roles in relation to cancer.
    Lancet (London, England), 1981, Jul-04, Volume: 2, Issue:8236

    Topics: 4-Butyrolactone; Bacteria; Butylene Glycols; Clostridium; Depression, Chemical; Female; Humans; Intestines; Lignans; Male; Menstruation; Metronidazole; Neoplasms; Oxytetracycline; Plant Extracts; Pregnancy

1981
Distribution of tumor-damaging lignans among conifers.
    Journal of the National Cancer Institute, 1957, Volume: 18, Issue:1

    Topics: Antineoplastic Agents; Humans; Lignans; Neoplasms; Plant Extracts; Tracheophyta

1957