lignans has been researched along with Colonic-Neoplasms* in 48 studies
3 review(s) available for lignans and Colonic-Neoplasms
Article | Year |
---|---|
Dietary lignans: potential role in cancer prevention.
Recent in vitro, animal, and epidemiological studies suggest that dietary lignans may be chemopreventive, potentially through anti-estrogenic, anti-angiogenic, pro- apoptotic, and anti-oxidant mechanisms. In this article, we review lignan food sources and metabolism, proposed anti-carcinogenic mechanisms, and the evidence for a role of lignans in breast, colon, and prostate cancer prevention from animal and epidemiologic literature. Although a number of in vitro and animal studies support a role for lignan-rich foods and purified lignans in the modulation of cancer events of the breast, prostate, and colon, epidemiological studies, sparse and often retrospective in nature, offer inconsistent findings. The most support for a role of lignans in cancer is observed for premenopausal breast cancer. Additional epidemiological studies that use a prospective design and well-developed food databases and questionnaires are needed to adequately evaluate the role of lignans in cancer prevention. Topics: Animals; Breast Neoplasms; Colonic Neoplasms; Diet; Female; Humans; Lignans; Male; Prostatic Neoplasms; Rats | 2005 |
Protection against cancer by wheat bran: role of dietary fibre and phytochemicals.
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 |
Western diet and Western diseases: some hormonal and biochemical mechanisms and associations.
Breast cancer, prostate cancer, coronary heart disease and colon cancer belong to the so-called Western diseases and a general opinion is that diet is a significant or even the main factor increasing incidence and mortality of these diseases in the Western world. This review describes studies carried out in this department for about 10 years, many in collaboration with scientists abroad, and with the aim to clarify some of the connections between the diet and sex hormone, lipid and bile acid metabolism. A Western-type diet elevates plasma levels of sex hormones and decreases the sex hormone binding globulin concentration, increasing the bioavailability of these steroids. The same diet results in low formation of mammalian lignans and isoflavonic phytoestrogens. These diphenolic compounds seem to affect hormone metabolism and production and cancer cell growth by many different mechanisms making them candidates for a role as cancer protective substances. The precursors of these diphenols are to be found in fiber-rich unrefined grain products, various seeds, beans and probably also in pulses, peas and berries. Some types of fiber seem to influence sex hormone and bile acid metabolism mainly by partial interruption of the enterohepatic circulation, by alteration of intestinal metabolism and by increasing fecal excretion of these compounds. The sex hormone pattern found in connection with a Western-type diet is prevailing in the breast cancer patients, but is only partly a result of the diet. Topics: Antineoplastic Agents, Phytogenic; Bile Acids and Salts; Breast Neoplasms; Colonic Neoplasms; Coronary Disease; Diet; Female; Gonadal Steroid Hormones; Humans; Isoflavones; Lignans; Lignin; Lipid Metabolism; Male; Neoplasms, Hormone-Dependent; Nutritional Physiological Phenomena | 1990 |
1 trial(s) available for lignans and Colonic-Neoplasms
Article | Year |
---|---|
Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue.
The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health. Topics: Adult; Biopsy; Colon; Colon, Sigmoid; Colonic Neoplasms; Cross-Over Studies; Double-Blind Method; Epithelial Cells; Epithelium; Extracellular Matrix; Female; Gene Expression Profiling; Humans; Intestinal Mucosa; Lignans; Male; Middle Aged; Rectum; RNA, Messenger; Transcriptome; Young Adult | 2016 |
44 other study(ies) available for lignans and Colonic-Neoplasms
Article | Year |
---|---|
Lignans and Polyphenols of Phyllanthus amarus Schumach and Thonn Induce Apoptosis in HCT116 Human Colon Cancer Cells through Caspases-Dependent Pathway.
The anticancer effects of Phyllanthus amarus extract on various cancer cells have been investigated, however, the effects of its major constituents on HCT116 human colorectal cancer cells have not been reported.. In the present study, we investigated the cytotoxic effect of 80% ethanol extract of P. amarus and its marker constituents (phyllanthin, hypophyllanthin, gallic acid, niranthin, greraniin, phyltetralin, isolintetralin, corilagin and ellagic acid) on HCT116 and their underlying mechanisms of action.. Their antiproliferative and apoptotic effects on HCT 116 were performed using MTT assay and flow cytometric analysis, respectively, while caspases 3/7, 8 and 9 activities were examined using the colorimetric method. The expression of cleaved poly ADP ribose polymerase enzyme (PARP) and cytochrome c proteins was investigated by the immune-blot technique.. HPLC and LC-MS/MS analyses demonstrated that the extract contained mainly lignans and polyphenols. The plant samples markedly suppressed the growth and expansion of HCT116 cells in a concentration- and time-dependent manner with no toxicity against normal human fibroblast CCD18 Co. P. amarus extract, phyllanthin and gallic acid induced mode of cell death primarily through apoptosis as confirmed by the exteriorization of phosphatidylserine. Caspases 3/7, 8, and 9 activities increased in a concentration-dependent manner following 24h treatment. The expressions of cleaved PARP (Asp 214) and cytochrome c were markedly upregulated.. P. amarus extract, phyllanthin and gallic acid exhibited an apoptotic effect on HCT116 cells through the caspases-dependent pathway. Topics: Apoptosis; Caspases; Cell Proliferation; Chromatography, Liquid; Colonic Neoplasms; Dose-Response Relationship, Drug; HCT116 Cells; Humans; Lignans; Phyllanthus; Plant Extracts; Polyphenols; Signal Transduction; Tandem Mass Spectrometry | 2021 |
Honokiol Affects Stem Cell Viability by Suppressing Oncogenic YAP1 Function to Inhibit Colon Tumorigenesis.
Honokiol (HNK) is a biphenolic compound that has been used in traditional medicine for treating various ailments, including cancers. In this study, we determined the effect of HNK on colon cancer cells in culture and in a colitis-associated cancer model. HNK treatment inhibited proliferation and colony formation while inducing apoptosis. In addition, HNK suppressed colonosphere formation. Molecular docking suggests that HNK interacts with reserve stem cell marker protein DCLK1, with a binding energy of -7.0 Kcal/mol. In vitro kinase assays demonstrated that HNK suppressed the DCLK1 kinase activity. HNK also suppressed the expression of additional cancer stem cell marker proteins LGR5 and CD44. The Hippo signaling pathway is active in intestinal stem cells. In the canonical pathway, YAP1 is phosphorylated at Ser127 by upstream Mst1/2 and Lats1/2. This results in the sequestration of YAP1 in the cytoplasm, thereby not allowing YAP1 to translocate to the nucleus and interact with TEAD1-4 transcription factors to induce gene expression. However, HNK suppressed Ser127 phosphorylation in YAP1, but the protein remains sequestered in the cytoplasm. We further determined that this occurs by YAP1 interacting with PUMA. To determine if this also occurs in vivo, we performed studies in an AOM/DSS induced colitis-associated cancer model. HNK administered by oral gavage at a dose of 5mg/kg bw for 24 weeks demonstrated a significant reduction in the expression of YAP1 and TEAD1 and in the stem marker proteins. Together, these data suggest that HNK prevents colon tumorigenesis in part by inducing PUMA-YAP1 interaction and cytoplasmic sequestration, thereby suppressing the oncogenic YAP1 activity. Topics: Adaptor Proteins, Signal Transducing; Animals; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers, Tumor; Biphenyl Compounds; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colitis; Colonic Neoplasms; Doublecortin-Like Kinases; Down-Regulation; Hippo Signaling Pathway; Humans; Intracellular Signaling Peptides and Proteins; Lignans; Male; Mice, Inbred ICR; Models, Biological; Neoplastic Stem Cells; Protein Binding; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Signal Transduction; Transcription Factors; Tumor Stem Cell Assay; YAP-Signaling Proteins | 2021 |
Schizandrin A exhibits potent anticancer activity in colorectal cancer cells by inhibiting heat shock factor 1.
Heat shock factor 1 (HSF1) is a powerful multifaceted oncogenic modifier that plays a role in maintaining the protein balance of cancer cells under various stresses. In recent studies, there have been reports of increased expression of HSF1 in colorectal cancer (CRC) cells, and the depletion of the HSF1 gene knockdown has inhibited colon cancer growth both in vivo and in vitro. Therefore, HSF1 is a promising target for colon cancer treatment and chemoprevention. In the present study, we found that Schizandrin A (Sch A) significantly inhibited the growth of CRC cell lines by inducing cell cycle arrest, apoptosis and death. Through HSE luciferase reporter assay and quantitative PCR (qPCR), we identified Sch A as a novel HSF1 inhibitor. In addition, Sch A could effectively inhibit the induction of HSF1 target proteins such as heat-shock protein (HSP) 70 (HSP70) and HSP27, whether in heat shock or normal temperature culture. In the Surface Plasmon Resonance (SPR) experiment, Sch A showed moderate affinity with HSF1, further confirming that Sch A might be a direct HSF1 inhibitor. The molecular docking and molecular dynamic simulation results of HSF1/Sch A suggested that Sch A formed key hydrogen bond and hydrophobic interactions with HSF1, which may contribute to its potent HSF1 inhibition. These findings provide clues for the design of novel HSF1 inhibitors and drug candidates for colon cancer treatment. Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; China; Colonic Neoplasms; Colorectal Neoplasms; Cyclooctanes; DNA-Binding Proteins; Heat Shock Transcription Factors; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Lignans; Molecular Docking Simulation; Polycyclic Compounds; Transcription Factors | 2020 |
Anti‑proliferative effect of honokiol on SW620 cells through upregulating BMP7 expression via the TGF‑β1/p53 signaling pathway.
Honokiol (HNK), a natural pharmaceutically active component extracted from magnolia bark, has been used for clinical treatments and has anti‑inflammatory, antiviral and antioxidative effects. In recent years, anticancer research has become a major hotspot. However, the underlying molecular mechanisms of how HNK inhibits colorectal cancer have remained elusive. The present study focused on elucidating the effects of HNK on the expression of bone morphogenetic protein (BMP)7 and its downstream interaction with transforming growth factor (TGF)‑β1 and p53 in colon cancer. In in vitro assays, cell viability, cell cycle distribution and apoptosis were examined using Cell Counting Kit‑8, flow cytometry and reverse transcription‑quantitative PCR, respectively. In addition, the expression of BMP7, TGF‑β1 and relevant signaling proteins was determined by western blot analysis. In vivo, the anticancer effect of HNK was assessed in xenografts in nude mice. Furthermore, immunohistochemistry was performed to evaluate the association between BMP7 and TGF‑β1 expression in colon cancer. The results indicated that HNK inhibited the proliferation of colon cancer cell lines, with SW620 cells being more sensitive than other colon cancer cell lines. Furthermore, HNK markedly promoted the expression of BMP7 at the mRNA and protein level. Exogenous BMP7 potentiated the effect of HNK on SW620 cells, while knocking down BMP7 inhibited it. As a downstream mechanism, HNK increased the expression of TGF‑β1 and p53, which was enhanced by exogenous BMP7 in SW620 cells. In addition, immunohistochemical analysis indicated a positive association between BMP7 and TGF‑β1 expression. Hence, the present results suggested that HNK is a promising agent for the treatment of colon cancer and enhanced the expression TGF‑β1 and p53 through stimulating BMP7 activity via the non‑canonical TGF‑β signaling pathway. Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Bone Morphogenetic Protein 7; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Female; Humans; Lignans; Mice; Mice, Nude; Signal Transduction; Transforming Growth Factor beta1; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays | 2020 |
Molecular dynamics of interaction of Sesamin and related compounds with the cancer marker β-catenin: an in silico study.
By virtue of their regulatory role in the biological process, certain protein-protein complexes form potential targets for designing and discovery of drugs. Alteration set in the controlled formation of such complexes results in dysregulation of several metabolic processes, leading to diseased condition. β-catenin/Tcf4 complex is one such protein-protein complex found altered in colorectal epithelial cells resulting in activation of target genes leading to cancer. Recently, certain lignans from seeds of the oil crop sesame were found inhibiting initiation and progression of this type of cancer. Molecular mechanism involved in the process, however, is not yet known. By an in silico study, we present here a possible mechanism of interaction between the sesame lignans and β-catenin leading to inhibition of formation of the said complex, thereby elevating some of these ligands as potential lead molecules in the development of drugs for treatment of colon cancer. To achieve this objective, we performed docking, molecular dynamics simulation, and binding free energy analysis of target-ligand complexes. Using computational alanine scanning approach, the key pocket residues of β-catenin that interact with Tcf4 in the formation of complex were identified. The test molecules were initially evaluated for their drug-like properties by application of Lipinski's rule of five. Results of this study revealed that Sesamin, a furofuran lignan from sesame, has the highest affinity for β-catenin particularly with its residues that interact with Tcf4 and thus serving as a potential lead molecule for development of a drug for colon cancer. Topics: beta Catenin; Binding Sites; Colonic Neoplasms; Computer Simulation; Dioxoles; Humans; Lignans; Models, Molecular; Molecular Docking Simulation; Protein Binding; Protein Conformation; Transcription Factor 4 | 2019 |
Schisandrin B prevents ulcerative colitis and colitis-associated-cancer by activating focal adhesion kinase and influence on gut microbiota in an in vivo and in vitro model.
Colitis-associated cancer (CAC) has a close relationship with ulcerative colitis (UC). Therapeutic effect of Schisandrin B (SchB) on UC and CAC remains largely unknown. We investigated the preventative effect of SchB on the dextran sulphate sodium (DSS) model of UC and azoxymethane (AOM)/DSS model of CAC. Furthermore, focal adhesion kinase (FAK) activation and influence on commensal microbiota are important for UC treatment. Impact on FAK activation by SchB in UC development was evaluated in vivo and vitro. We also conducted 16S rRNA sequencing to detect regulation of gut microbiota by SchB. Enhanced protection of intestinal epithelial barrier by SchB through activating FAK contributed to protective effect on colon for the fact that protection of SchB can be reversed by inhibition of FAK phosphorylation. Furthermore, influence on gut microbiota by SchB also played a significant role in UC prevention. Our results revealed that SchB was potent to prevent UC by enhancing protection of intestinal epithelial barrier and influence on gut microbiota, which led to inhibition of CAC. SchB was potential to become a new treatment for UC and prevention of CAC. Topics: Animals; Caco-2 Cells; Colitis, Ulcerative; Colonic Neoplasms; Cyclooctanes; Cytoprotection; Enzyme Activation; Focal Adhesion Protein-Tyrosine Kinases; Gastrointestinal Microbiome; HCT116 Cells; Humans; Intestinal Mucosa; Lignans; Male; Mice; Mice, Inbred C57BL; Permeability; Polycyclic Compounds; Signal Transduction | 2019 |
Arctigenin Inhibits Etoposide Resistance in HT-29 Colon Cancer Cells during Microenvironmental Stress.
Microenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase IIα, rendering cells resistant to topoisomerase IIα-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase IIα degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an IC Topics: Antineoplastic Agents; Apoptosis; Cell Survival; Colonic Neoplasms; Colony-Forming Units Assay; DNA Topoisomerases, Type II; Drug Resistance, Neoplasm; Endoplasmic Reticulum Chaperone BiP; Etoposide; Furans; Heat-Shock Proteins; HT29 Cells; Humans; Lignans; Stress, Physiological; Tumor Microenvironment | 2019 |
Serum enterolactone concentrations are low in colon but not in rectal cancer patients.
The dietary lignan metabolite, enterolactone, has been suggested to have anti-cancer functions, and high serum enterolactone concentrations have been associated with decreased risk of breast and prostate cancers. We hypothesized that serum enterolactone concentrations as a marker of plant-based foods are associated with decreased risk in colorectal cancer (CRC). We measured serum enterolactone glucuronide and sulfate concentrations by liquid chromatography-tandem mass spectrometry in 115 CRC patients and 76 sex- and age-matched controls and analyzed the results with respect to tumor parameters, clinical parameters, and systemic inflammatory markers. Patients with colon cancer had significant lower serum enterolactone glucuronide and sulfate concentrations than controls (glucuronide: median 3.14 nM vs. 6.32 nM, P < 0.001; sulfate: median 0.13 nM vs. 0.17 nM, P = 0.002), whereas rectal cancer patients had similar enterolactone levels as controls (glucuronide: median 5.39 nM vs. 6.32 nM, P = 0.357; sulfate: median 0.19 nM vs. 0.17 nM, P = 0.452). High serum enterolactone concentrations were associated with low tumor grade, high serum creatinine levels, and concomitant diabetes. In summary, our results suggest that serum enterolactone concentrations are decreased in colon but not in rectal cancer. Further investigations are required to assess whether this reflects an altered lignan metabolism by the colon microbiome. Topics: 4-Butyrolactone; Aged; Case-Control Studies; Colon; Colonic Neoplasms; Diet, Western; Dietary Fiber; Feeding Behavior; Female; Gastrointestinal Microbiome; Healthy Volunteers; Humans; Intestinal Mucosa; Lignans; Male; Middle Aged; Rectal Neoplasms; Rectum; Risk Factors | 2019 |
RETRACTED: Schizandrin A enhances chemosensitivity of colon carcinoma cells to 5-fluorouracil through up-regulation of miR-195.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ \ This article has been retracted at the request of the Editor-in-Chief.\ \ Given the comments of Dr Elisabeth Bik regarding this article “This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels”, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article. Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Cyclooctanes; Drug Resistance, Neoplasm; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Lignans; MicroRNAs; NF-kappa B; Phosphatidylinositol 3-Kinases; Polycyclic Compounds; Proto-Oncogene Proteins c-akt; Signal Transduction; Up-Regulation | 2018 |
Optimized conversion of antiproliferative lignans pinoresinol and epipinoresinol: Their simultaneous isolation and identification by centrifugal partition chromatography and high performance liquid chromatography.
High amount of the valuable lignan pinoresinol (PR) was determined in Carduus nutans fruit (7.8mg/g) for the first time. A preparative separation method using two consecutive, identical steps of centrifugal partition chromatography (CPC) was developed in order (i) to isolate PR and (ii) to subsequently isolate PR and its 7' epimer epipinoresinol (EPR) simultaneously after an optimized acid treatment which resulted in PR epimerization forming equal amounts of PR and EPR, from C. nutans fruit. As optimal conditions, a two-phase solvent system consisting of methyl tert-butyl ether:acetone:water (4:3:3, v/v/v) for CPC separation, and an acid treatment performed at 50°C for 30min for the epimerization were applied. Thus, 33.7mg and 32.8mg PR and EPR, in as high as 93.7% and 92.3% purity, were isolated from 10.0gC. nutans fruit, representing 86.4% and 84.1% efficiency, respectively. Conversion characteristic of PR and EPR in acidic medium, determined as a function of time and temperature of acid treatment provides their unambiguous identification by on-line high performance liquid chromatography (HPLC). Antiproliferative assay of isolated PR and EPR in two different types of colon cancer cell lines (HCT116 and SW480) confirmed that both epimers caused a more significant decrease of viability in HCT116 cells than in SW480 cells, suggesting their similar mechanism of antiproliferative action. Topics: Antineoplastic Agents, Phytogenic; Carduus; Cell Proliferation; Chromatography, High Pressure Liquid; Colonic Neoplasms; Fruit; Furans; Gas Chromatography-Mass Spectrometry; HCT116 Cells; Humans; Lignans; Plant Extracts; Stereoisomerism | 2017 |
BMP7 mediates the anticancer effect of honokiol by upregulating p53 in HCT116 cells.
Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner. HNK activates p53 in HCT116 and other colon cancer cells. Exogenous p53 potentiates the anticancer of HNK, while p53 inhibitor decreases this effect of HNK. Moreover, HNK upregulates the expression of bone morphogenetic protein 7 (BMP7) in colon cancer cells; Exogenous BMP7 enhances the anticancer activity of HNK and BMP7 specific antibody reduces this effect of HNK. For mechanism, we found that HNK cannot increase the level of Smad1/5/8; Exogenous BMP7 potentiates the HNK-induced activation of p53. On the contrary, BMP7 specific antibody inhibits the HNK-induced activation of p53 in colon cancer cells and partly decreases the total level of p53. Our findings suggested that HNK may be a promising anticancer drug for CRC; activation of p53 plays an important role in the anticancer activity of HNK, which may be initialized partly by the HNK-induced upregulation of BMP7. Topics: Apoptosis; Biphenyl Compounds; Bone Morphogenetic Protein 7; Cell Proliferation; Cell Survival; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Lignans; Signal Transduction; Smad Proteins; Tumor Suppressor Protein p53 | 2017 |
Taiwanin E inhibits cell migration in human LoVo colon cancer cells by suppressing MMP-2/9 expression via p38 MAPK pathway.
Taiwanin E is a natural compound which is structurally analogous to estrogen II and is abundantly found in Taiwania cryptomerioides. It has been previously reported for its anticancer effects; however, the pharmaceutical effect of Taiwanin E on Human LoVo colon cancer cells is not clear. In this study, we investigated the effects of Taiwanin E on metastasis and the associated mechanism of action on Human LoVo colon cancer cells with respect to the modulations in their cell migration and signaling pathways associated with migration. The results showed that Taiwanin E inhibited cell migration ability correlated with reduced expression and activity of MMP-2 and MMP-9. In addition, Taiwanin E induced activation of p38 through phosphorylation. Inhibition of p38α/β significantly abolished the effect of Taiwanin E on cell migration and MMP-2/-9 activity. Our results conclude that Taiwanin E inhibited cell migration chiefly via p38α MAPK pathway and in a lesser extend via p38β MAPK. The results elucidate the potential of the phytoestrogen natural compound Taiwanin E as a cancer therapeutic agent in inhibiting the cell migration. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2021-2031, 2017. Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Movement; Colonic Neoplasms; Humans; Lignans; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; p38 Mitogen-Activated Protein Kinases; Phosphorylation | 2017 |
Evaluation of lignan (-)-cubebin extracted from Piper cubeba on human colon adenocarcinoma cells (HT29).
The dibenzylbutyrolactone lignan (-)-cubebin, which is extracted from the seeds of the pepper Piper cubeba, has shown promise as an anti-inflammatory, analgesic, leishmanicidal, antiproliferative, and trypanocidal compound. Given the therapeutic potential of (-)-cubebin, this study aimed to investigate its safety profile by analyzing cytotoxicity, mutagenicity, cell proliferation kinetics, induction of apoptosis, and expression of pro-apoptotic genes in human colon adenocarcinoma cells (HT29) exposed to (-)-cubebin. MTT cytotoxicity assays demonstrated that (-)-cubebin was cytotoxic only at 280 µM, whereas it was not cytotoxic at 2.8, 14, or 28 µM. Data demonstrated that (-)-cubebin was not mutagenic as evidenced by a micronucleus (MN) assay, did not alter cell-growth kinetics over 4 d, and showed absence of induced apoptosis after 24 h. Further, CASP8 and CASP9 gene expression was not markedly changed in HT29 cells exposed to 28 µM or 70 µM (-)-cubebin for 12 h. Based on our observations, (-)-cubebin was cytotoxic at a concentration of 280 µM, suggesting that the use of this concentration should be avoided. However, lower concentrations exerted no apparent damaging effects, indicating that this lignan is safe to use for pharmacological purposes at certain concentrations. Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 8; Caspase 9; Cell Proliferation; Cell Survival; Colonic Neoplasms; DNA; HT29 Cells; Humans; Lignans; Micronucleus Tests; Piper | 2016 |
Endogenous enzyme-hydrolyzed fruit of Cirsium brachycephalum: optimal source of the antiproliferative lignan trachelogenin regulating the Wnt/β-catenin signaling pathway in the SW480 colon adenocarcinoma cell line.
The molecular constituents of Cirsium brachycephalum fruits were identified, quantified and isolated for the first time. The lignan glycoside tracheloside was the main compound, which was transformed quantitatively into its aglycone trachelogenin by endogenous enzymatic treatment of the fruit. Following this transformation by high performance liquid chromatography (HPLC) hyphenated with UV and mass spectrometry (MS) detections on a quantitative basis, the enzyme-hydrolyzed fruit was found to be the richest raw material containing trachelogenin (17.2mg/g) reported to date. Thus, the enzyme-hydrolyzed fruit was used to isolate trachelogenin using preparative HPLC in order to (1) unambiguously confirm its identity by gas chromatography-MS, nuclear magnetic resonance spectroscopy and optical rotation, and (2) investigate its in vitro antiproliferative activities against the SW480 colon adenocarcinoma cell line. Trachelogenin significantly affected the phosphorylation of key proteins such as β-Catenin, c-Myc and GSK3 in the β-Catenin signaling pathway in a concentration-dependent manner. These changes account for the antiproliferative effects of trachelogenin. Topics: 4-Butyrolactone; Adenocarcinoma; Antineoplastic Agents, Phytogenic; beta Catenin; Cell Line, Tumor; Cirsium; Colonic Neoplasms; Fruit; Glycogen Synthase Kinase 3; Humans; Lignans; Molecular Structure; Proto-Oncogene Proteins c-myc; Wnt Signaling Pathway | 2015 |
Synthesis of tetrahydrohonokiol derivates and their evaluation for cytotoxic activity against CCRF-CEM leukemia, U251 glioblastoma and HCT-116 colon cancer cells.
Biphenyl neolignans such as honokiol and magnolol, which are the major active constituents of the Asian medicinal plant Magnolia officinalis, are known to exert a multitude of pharmacological and biological activities. Among these, cytotoxic and tumor growth inhibitory activity against various tumour cell lines are well-documented. To further elucidate the cytotoxic effects of honokiol derivatives, derivatizations were performed using tetrahydrohonokiol as a scaffold. The derivatizations comprised the introduction of functional groups, e.g., nitro and amino groups, as well as alkylation. This way, 18 derivatives, of which 13 were previously undescribed compounds, were evaluated against CCRF-CEM leukemia cells, U251 glioblastoma and HCT-116 colon cancer cells. The results revealed no significant cytotoxic effects in any of the three tested cell lines at a test concentration of 10 µM. Topics: Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cell Survival; Colonic Neoplasms; Drug Screening Assays, Antitumor; Glioblastoma; HCT116 Cells; Humans; Inhibitory Concentration 50; Leukemia; Lignans; Methylation; Microwaves | 2014 |
In vitro effects of extracts of extra virgin olive oil on human colon cancer cells.
The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular diseases, and some types of cancer. Recent interest has been focused on the biological activity of phenolic compounds present in extra virgin olive oils (EVOOs). Both in vivo and in vitro studies have shown that EVOO components have positive effects on metabolic parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet function, and antimicrobial activity. We have investigated the possible interactions between 2 extracts of extra virgin olive oil and estrogen receptor β (ERβ) in an in vitro model of colon cancer. The qualification and quantification of the components of the 2 samples tested showed that phenolic compounds-hydroxytyrosol, secoiridoids, and lignans-are the major represented compounds. EVOO extracts were tested on a colon cancer cell line engineered to overexpress ERβ (HCT8-β8). By using custom made Oligo microarray, gene expression profiles of colon cancer cells challenged with EVOO-T extracts when compared with those of cells exposed to 17β-estradiol (17β-E2). This study demonstrated that the EVOO extracts tested showed an antiproliferative effect on colon cancer cells through the interaction with estrogen-dependent signals involved in tumor cell growth. Specifically, the ability of EVOO extracts to inhibit cell proliferation was superimposable to the activation of the ERβ receptor, similar to what was observed after 17β-E2 challenge. Topics: Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Estradiol; Estrogen Receptor beta; Humans; Lignans; Oligonucleotide Array Sequence Analysis; Olive Oil; Plant Oils; Polyphenols; Transcriptome | 2014 |
Inhibition of angiogenesis: a novel antitumor mechanism of the herbal compound arctigenin.
Arctigenin, a functional ingredient of several traditional Chinese herbs, has been reported to have potential antitumor activity. However, its mechanisms of action are still not well elucidated. Because the establishment and metastatic spread of tumors is crucially dependent on angiogenesis, here we investigated whether arctigenin inhibits tumor growth by disturbing blood vessel formation. For this purpose, human dermal microvascular endothelial cells were exposed to different arctigenin doses to study their viability, proliferation, protein expression, migration, and tube formation compared with vehicle-treated controls. In addition, arctigenin action on vascular sprouting was analyzed in an aortic ring assay. Furthermore, we studied direct arctigenin effects on CT26.WT colon carcinoma cells. Spheroids of these tumor cells were transplanted into the dorsal skinfold chamber of arctigenin-treated and vehicle-treated BALB/c mice for the in-vivo analysis of tumor vascularization and growth by intravital fluorescence microscopy, histology, and immunohistochemistry. We found that noncytotoxic doses of arctigenin dose dependently reduced the proliferation of human dermal microvascular endothelial cells without affecting their migratory and tube-forming capacity. Arctigenin treatment also resulted in a decreased cellular expression of phosphorylated serine/threonine protein kinase AKT, vascular endothelial growth factor receptor 2, and proliferating cell nuclear antigen and inhibited vascular sprouting from aortic rings. In addition, proliferation, but not secretion of vascular endothelial growth factor, was decreased in arctigenin-treated tumor cells. Finally, arctigenin suppressed the vascularization and growth of engrafting CT26.WT tumors in the dorsal skinfold chamber model. Taken together, these results show for the first time an antiangiogenic action of arctigenin, which may contribute considerably toward its antitumor activity. Topics: Angiogenesis Inhibitors; Angiogenic Proteins; Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Endothelial Cells; Furans; Humans; Immunohistochemistry; Lignans; Male; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Neovascularization, Pathologic; Neovascularization, Physiologic; Phytotherapy; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Signal Transduction; Spheroids, Cellular; Time Factors; Tissue Culture Techniques; Tumor Burden | 2013 |
Honokiol augments the anti-cancer effects of oxaliplatin in colon cancer cells.
Oxaliplatin is an important drug in the chemotherapy of colorectal carcinoma, but its toxicity, especially dose-related neurosensory toxicity, is not well tolerated. In this study, we investigated whether honokiol could augment the anti-tumor effect of oxaliplatin in colon cancer HT-29 cells in vitro and whether honokiol could be used with oxaliplatin to decrease oxaliplatin dose. We used the normal colon cells, human colonic epithelial cells (HCoEpiCs) as control cells. Cell proliferation, apoptosis, prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) levels were also investigated. Expression levels of cyclo-oxygenase 2 (COX-2), VEGF, AKT/p-AKT, extracellular signal-related kinase (ERK)1/2/p-ERK1/2, nuclear factor kappa B (NF-κB) P65/p-P65, and caspase-3 were measured. Honokiol or oxaliplatin suppressed the proliferation of HT-29 cells in a concentration-dependent manner, but only high concentrations of honokiol would suppress the proliferation of HCoEpiCs. HT-29 cells were more sensitive to oxaliplatin treatment in the presence of honokiol. Oxaliplatin combined with honokiol improved the apoptosis rate of HT-29 cell and reduced PGE2 and VEGF secretion levels. Expression levels of COX-2 and VEGF protein and phosphorylation of AKT, ERK1/2, and NF-κB P65 were also inhibited. Caspase-3 levels were upregulated after honokiol treatment. Therefore, honokiol can be used in combination with oxaliplatin in the chemotherapy of colon cancer. This combination allows a reduction in oxaliplatin dose, and thereby reduces its adverse effects. It may also enhance the chemotherapeutic effect of oxaliplatin for this disease. Topics: Antineoplastic Agents; Apoptosis; Biphenyl Compounds; Blotting, Western; Caspase 3; Cell Line; Cell Proliferation; Cell Survival; Colonic Neoplasms; Cyclooxygenase 2; Dinoprostone; Dose-Response Relationship, Drug; Drug Synergism; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Extracellular Signal-Regulated MAP Kinases; HT29 Cells; Humans; Lignans; NF-kappa B; Organoplatinum Compounds; Oxaliplatin; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A | 2013 |
Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the suppression of Wnt/β-catenin signaling pathway in colon cancer cells.
Based on the Wnt inhibitors as potential targets in the development of anticancer agents, natural compounds were evaluated for β-catenin-mediated transcriptional activity. A natural lignan hydnocarpin isolated from Lonicera japonica was considered a potential inhibitor for Wnt/β-catenin signalings. The anti-proliferative activity of hydnocarpin was also found to be associated with the suppression of Wnt/β-catenin-mediated signaling pathway in human colon cancer cells. These data suggest that hydnocarpin might be a novel Wnt inhibitor and has a potential of signaling regulator in β-catenin-mediated signaling pathways. Topics: Antineoplastic Agents, Phytogenic; Axin Protein; beta Catenin; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Flavonolignans; Humans; Lignans; Lonicera; RNA Interference; RNA, Small Interfering; Wnt Proteins; Wnt Signaling Pathway | 2013 |
4-O-methylhonokiol inhibits colon tumor growth via p21-mediated suppression of NF-κB activity.
Biphenolic components in the Magnolia family have shown several pharmacological activities such as antitumor effects. This study investigated the effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, on human colon cancer cell growth and its action mechanism. 4-O-methylhonokiol (0-30 μM) decreased constitutive activated nuclear factor (NF)-κB DNA binding activity and inhibited growth of human colon (SW620 and HCT116) cancer cells. It also caused G₀-G₁ phase cell cycle arrest followed by an induction of apoptotic cell death. However, knockdown with small interfering RNA (siRNA) of p21 or transfection with cyclin D1/Cdk4 binding site-mutated p21 abrogated MH-induced cell growth inhibition, inhibition of NF-κB activity as well as expression of cyclin D1 and Cdk4. Conversely, inhibition of NF-κB with specific inhibitor or siRNA augmented MH-induced apoptotic cell death. 4-O-methylhonokiol inhibited tumor growth, NF-κB activity and expression of antiapoptotic proteins; however, it increased the expression of apoptotic proteins as well as p21 in xenograft nude mice bearing SW620 cancer cells. The present study reveals that MH causes p21-mediated human colon cancer cell growth inhibition through suppression of NF-κB and indicates that this compound by itself or in combination with other anticancer agents could be useful for the treatment of cancer. Topics: Animals; Apoptosis; Biphenyl Compounds; Cell Cycle Checkpoints; Cell Proliferation; Colon; Colonic Neoplasms; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p21; Gene Knockdown Techniques; HCT116 Cells; Humans; Lignans; Magnolia; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Plant Extracts; RNA, Small Interfering | 2012 |
Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells.
Cancer stem cells are implicated in resistance to ionizing radiation (IR) and chemotherapy. Honokiol, a biphenolic compound has been used in traditional Chinese medicine for treating various ailments. In this study, we determined the ability of honokiol to enhance the sensitivity of colon cancer stem cells to IR. The combination of honokiol and IR suppressed proliferation and colony formation while inducing apoptosis of colon cancer cells in culture. There were also reduced numbers and size of spheroids, which was coupled with reduced expression of cancer stem cell marker protein DCLK1. Flow cytometry studies confirmed that the honokiol-IR combination reduced the number of DCLK1+ cells. In addition, there were reduced levels of activated Notch-1, its ligand Jagged-1, and the downstream target gene Hes-1. Furthermore, expression of components of the Notch-1 activating γ-secretase complex, presenilin 1, nicastrin, Pen2, and APH-1 was also suppressed. On the other hand, the honokiol effects were mitigated when the Notch intracellular domain was expressed. To determine the effect of honokiol-IR combination on tumor growth in vivo, nude mice tumor xenografts were administered honokiol intraperitoneally and exposed to IR. The honokiol-IR combination significantly inhibited tumor xenograft growth. In addition, there were reduced levels of DCLK1 and the Notch signaling-related proteins in the xenograft tissues. Together, these data suggest that honokiol is a potent inhibitor of colon cancer growth that targets the stem cells by inhibiting the γ-secretase complex and the Notch signaling pathway. These studies warrant further clinical evaluation for the combination of honokiol and IR for treating colon cancers. Topics: Animals; Apoptosis; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Combined Modality Therapy; Down-Regulation; Drugs, Chinese Herbal; HCT116 Cells; Humans; Immunohistochemistry; Lignans; Male; Mice; Mice, Nude; Neoplastic Stem Cells; Nitric Oxide Synthase; Signal Transduction; Transfection; Xenograft Model Antitumor Assays | 2012 |
Magnolol-induced apoptosis in HCT-116 colon cancer cells is associated with the AMP-activated protein kinase signaling pathway.
Colon cancer is the third most common malignancy around the world. Surgery, chemotherapy, and radiotherapy are generally used to treat colon cancer, but no effective therapy for advanced colon carcinoma is available. Therefore, there is a need to identify other therapeutic agents against this disease. Magnolol, a hydroxylated biphenyl compound present in Magnolia officinalis, exerts anticancer potential and low toxicity. Emerging evidence has suggested that activation of AMP-activated protein kinase (AMPK), a potential cancer therapeutic target is involved in apoptosis in colon cancer cells. However, the effects of magnolol on human colon cancer through activation of AMPK remain unexplored. In this study, we explored whether magnolol exerts an antiproliferative effect, and induces apoptosis in HCT-116 human colon cancer cells. Magnolol displayed several apoptotic features, including propidium iodide labeling, DNA fragmentation, and caspase-3 and poly(ADP-ribose) polymerase cleavages. We showed that magnolol induced the phosphorylation of AMPK in dose- and time-dependent manners. The selective AMPK inhibitor compound C abrogated the effect of magnolol on AMPK activation, suppression of proliferation, and caspase-3 cleavage. Magnolol downregulated expression of the antiapoptotic protein Bcl2, upregulated expression of pro-apoptotic protein p53 and Bax, and caused the release of mitochondrial cytochrome c. Magnolol-induced p53 and Bcl2 expression was abolished in the presence of compound C. Magnolol inhibited migration and invasion of HCT-116 cells through AMPK activation. These findings demonstrate that AMPK mediates the anticancer effects of magnolol through apoptosis in HCT-116 cells. Topics: AMP-Activated Protein Kinases; Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Biphenyl Compounds; Caspase 3; Cell Movement; Colonic Neoplasms; Cytochromes c; DNA Fragmentation; Dose-Response Relationship, Drug; HCT116 Cells; Humans; Lignans; Magnolia; Mitochondria; Phosphorylation; Phytotherapy; Plant Extracts; Poly(ADP-ribose) Polymerases; Propidium; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Tumor Suppressor Protein p53 | 2012 |
Phenethyl caffeate benzo[kl]xanthene lignan with DNA interacting properties induces DNA damage and apoptosis in colon cancer cells.
Phenethyl caffeate benzoxanthene lignan (PCBL) is a synthetic compound with DNA interacting, antiangiogenic, antiproliferative and tumor cell death inducing abilities. Though PCBL exhibits the qualities of a prospective antitumor agent, the basic mechanism of PCBL induced cell death remains unknown. This study aims to analyze the molecular mechanisms of PCBL induced cell death in tumor cells to further substantiate its antitumor abilities.. MTT assay was used for finding cell proliferation inhibition, flow cytometric analysis for the detection of cell cycle arrest, comet assay for DNA break detection and immunofluorescence for analyzing H2AX phosphorylation. Western blot analysis was used to detect the activation of different proteins related to DNA damage response and apoptosis.. PCBL inhibited proliferation of WiDr cells more efficiently than its analog, MCBL. Comet analysis of PCBL treated WiDr cells and activity of various DNA damage response proteins such as γ-H2AX, BRCA1, ATR and Chk1 in PCBL treated cells demonstrated the DNA damaging property of PCBL. Effector molecules of apoptosis such as caspase-3, caspase-7 and caspase-9 were found activated along with PARP cleavage in PCBL treated cells, suggesting apoptosis as the main mode of cell death. PCBL induced cell death was found associated with the activation of MAPK signaling. Inhibition of ERK, one of the MAPKs, by U0126 improved the apoptosis inducing ability of PCBL.. In vitro findings suggest that PCBL works by initiating DNA damage and inducing apoptosis in cancer cells and thus could be considered for further preclinical studies. Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Blotting, Western; Caspases; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Comet Assay; DNA Damage; Flow Cytometry; Fluorescent Antibody Technique; Humans; Lignans; MAP Kinase Signaling System | 2012 |
Sesamin induces autophagy in colon cancer cells by reducing tyrosine phosphorylation of EphA1 and EphB2.
Receptor tyrosine kinase EphB2 and autophagic machinery are known as tumor suppressors; however, the connection remains to be elucidated. Here, we show the link between EphB2 and autophagy. Sesamin, a major lignan in sesame oil, induced autophagy in the human colon cancer cell lines HT29 and LS180, as shown by electron microscopy, as well as Western blotting and immunofluorescence imaging using an anti-LC3 antibody. Receptor tyrosine kinase array analysis revealed that sesamin treatment increased the levels of unphosphorylated -EphA1 and -EphB2 in HT29 cells. Silencing of EphA1 and EphB2 blocked sesamin-induced autophagy as well as sesamin-induced loss of cell viability. These results show that EphA1 and EphB2 play a critical role in this process. The present study reveals a novel function for EphA1 and EphB2 in the induction of autophagy, suggesting a tumor suppressor role for these proteins in colorectal cancer. Topics: Antineoplastic Agents; Autophagy; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Dioxoles; Gene Silencing; HT29 Cells; Humans; Lignans; Phosphorylation; Receptor, EphA1; Receptor, EphB2; Tyrosine | 2011 |
A compound isolated from Schisandra chinensis induces apoptosis.
Schizandra chinensis has been known to have five predominant tastes: salty, sweet, sour, astringent, and bitter. It has also been shown to have various effects on the cardiovascular system, gastrointestinal system, anti-inflammatory, central nervous system, endocrine system, and stress protect. However, its anti-cancer activity on colon carcinoma HCT-116 cells has not been yet been examined. Thus, in this study, we attempted to isolate a compound from Schisandra chinensis that induced apoptosis in HCT-116 cells. An active compound was found and identified to be Gomisin A. It displayed apoptotic activity through caspase-7 cleavage in colon carcinoma HCT-116 cells. In addition, we further assessed the effects of this compound using long-term survival clonogenic assay with HCT116 cells. Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 7; Colonic Neoplasms; Cyclooctanes; Dioxoles; HCT116 Cells; Humans; Lignans; Schisandra | 2011 |
Plasma enterolactone and risk of colon and rectal cancer in a case-cohort study of Danish men and women.
This case-cohort study examined the association between plasma enterolactone concentration and incidence of colon and rectal cancer in the Diet, Cancer and Health cohort, which enrolled 57,053 participants aged 50-64. Information about diet and lifestyle was obtained by questionnaire, and data on prescriptions of antibiotics were obtained from the Danish Prescription Registry. Cases diagnosed during 5.9 years of follow-up and a randomly selected sample of the cohort had a plasma sample analyzed for enterolactone by time-resolved fluoro-immuno assay. Associations were analyzed by Cox proportional hazards model. A total of 244 colon cancer cases, 137 rectal cancer cases, and 370 sub-cohort members were included in the statistical analyses. For each doubling in enterolactone concentration, we found lower risk of colon cancer among women [IRR (95% CI) = 0.76 (0.60-0.96)] and a tendency toward lower risk of rectal cancer [IRR (95% CI) = 0.83 (0.60-1.14)]. Among men, a doubling in enterolactone tended to be associated with higher risk of colon cancer [IRR (95% CI) = 1.09 (0.89-1.34)] and was associated with statistically significantly higher risk of rectal cancer [IRR (95% CI) = 1.74 (1.25-2.44)]. Exclusion of antibiotics users strengthened the results slightly. In conclusion, with higher enterolactone levels, we found lower risk of colon cancer among women and higher risk of rectal cancer among men. Topics: 4-Butyrolactone; Case-Control Studies; Cohort Studies; Colonic Neoplasms; Denmark; Feeding Behavior; Female; Humans; Life Style; Lignans; Male; Middle Aged; Phytoestrogens; Rectal Neoplasms; Risk Factors | 2010 |
Phenolic compounds as selective antineoplasic agents against multidrug-resistant human cancer cells.
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 |
Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity.
Cancer cells in poorly vascularized solid tumors are constantly or intermittently exposed to stressful microenvironments, including glucose deprivation, hypoxia, and other forms of nutrient starvation. These tumor-specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose-deprived conditions. Here we identify arctigenin (ARC-G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC-G blocked expression of UPR target genes such as phosphorylated-PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2 alpha during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase-9 and -3. Furthermore, ARC-G suppressed tumor growth of colon cancer HT-29 xenografts. Our results demonstrate that ARC-G can be served as a novel type of antitumor agent targeting the UPR in glucose-deprived solid tumors. Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Endoplasmic Reticulum Chaperone BiP; Furans; Gene Expression Regulation, Neoplastic; Glucose; HeLa Cells; HT29 Cells; Humans; Lignans; Mice; Mice, Nude; Time Factors; Tumor Burden; Unfolded Protein Response; Xenograft Model Antitumor Assays | 2010 |
Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization.
This study aims to develop self-assembled poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles to encapsulate hydrophobic honokiol (HK) in order to overcome its poor water solubility and to meet the requirement of intravenous administration. Honokiol loaded micelles (HK-micelles) were prepared by self-assembly of PECE copolymer in aqueous solution, triggered by its amphiphilic characteristic assisted by ultrasonication without any organic solvents, surfactants and vigorous stirring. The particle size of the prepared HK-micelles measured by Malvern laser particle size analyzer were 58 nm, which is small enough to be a candidate for an intravenous drug delivery system. Furthermore, the HK-micelles could be lyophilized into powder without any adjuvant, and the re-dissolved HK-micelles are stable and homogeneous with particle size about 61 nm. Furthermore, the in vitro release profile showed a significant difference between the rapid release of free HK and the much slower and sustained release of HK-micelles. Moreover, the cytotoxicity results of blank micelles and HK-micelles showed that the PECE micelle was a safe carrier and the encapsulated HK retained its potent antitumor effect. In short, the HK-micelles were successfully prepared by an improved method and might be promising carriers for intravenous delivery of HK in cancer chemotherapy, being effective, stable, safe (organic solvent and surfactant free), and easy to produce and scale up. Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Biphenyl Compounds; Cell Growth Processes; Cell Line, Tumor; Colonic Neoplasms; Drug Delivery Systems; Drug Screening Assays, Antitumor; Drug Stability; Drugs, Chinese Herbal; Humans; Lignans; Lung Neoplasms; Mice; Micelles; Microscopy, Electron, Transmission; Particle Size; Polyesters; Polyethylene Glycols; Solubility; Sonication; X-Ray Diffraction | 2010 |
Cytostatic inhibition of cancer cell growth by lignan secoisolariciresinol diglucoside.
Our previous study demonstrated that lignan metabolites enterolactone and enterodiol inhibited colonic cancer cell growth by inducing cell cycle arrest and apoptosis. However, the dietary lignans are naturally present as glycoside precursors, such as secoisolariciresinol diglucoside (SDG), which have not been evaluated yet. This study tested the hypothesis that dietary SDG might have a different effect than its metabolites in human colonic SW480 cancer cells. Treatment with SDG at 0 to 40 μmol/L for up to 48 hours resulted in a dose- and time-dependent decrease in cell numbers, which was comparable to enterolactone. The inhibition of cell growth by SDG did not appear to be mediated by cytotoxicity, but by a cytostatic mechanism associated with an increase of cyclin A expression. Furthermore, high-performance liquid chromatography analysis indicated that SDG in the media was much more stable than enterolactone (95% of SDG survival vs 57% of enterolactone after 48-hour treatment). When the cells were treated with either enterolactone or SDG at 40 μmol/L for 48 hours, the intracellular levels of enterolactone, as measured by high-performance liquid chromatography-mass spectrometry/electron spray ionization, were about 8.3 × 10(-8) nmol per cell; but intracellular SDG or potential metabolites were undetectable. Taken together, SDG demonstrated similar effects on cell growth, cytotoxicity, and cell cycle arrest when compared with its metabolite enterolactone. However, the reliable stability and undetectable intracellular SDG in treated cells may suggest that metabolism of SDG, if exposed directly to the colonic cells, could be different from the known degradation by microorganisms in human gut. Topics: 4-Butyrolactone; Adenocarcinoma; Anticarcinogenic Agents; Butylene Glycols; Cell Cycle; Cell Line, Tumor; Chromatography, High Pressure Liquid; Colonic Neoplasms; Cyclin A; Cytostatic Agents; Dietary Carbohydrates; Dose-Response Relationship, Drug; Glucosides; Glycosides; Humans; Lignans; Mass Spectrometry | 2010 |
Effects of dietary flaxseed on intestinal tumorigenesis in Apc(Min) mouse.
Dietary flaxseed has been shown to prevent azoxymethane (AOM)-induced colorectal cancers in male Fisher rats. The present study was designed to investigate the chemopreventive effects of dietary flaxseed on the development of intestinal tumors in Apc(Min) mice. Apc(Min) mice were divided into five different groups, fed with control (AIN-93M meal), corn meal, flaxseed meal, corn oil, and flaxseed oil supplemented diets. Results showed that dietary flaxseed significantly decreased (P < 0.05) tumor multiplicity and size in the small intestine and colon as compared to control, corn-treated groups. Intestine, colon, and serum samples of corn-treated groups showed higher levels of omega -6 fatty acids, whereas the flaxseed treated groups exhibited higher levels of omega -3 fatty acids. Lignans were detected in the serum, intestine, and colon samples for flaxseed meal group. COX-1 and COX-2 expression in the colon samples from the flaxseed meal group were significantly lower (P < 0.05) as compared to the corn meal group. Dietary flaxseed may be chemopreventive for intestinal tumor development in Apc(Min) mice possibly by increasing omega -3 fatty acid levels, lignans, and decreasing COX-1 and COX-2 levels. Topics: Adenomatous Polyposis Coli; alpha-Linolenic Acid; Animals; Anticarcinogenic Agents; Apoptosis; Azoxymethane; Colon; Colonic Neoplasms; Corn Oil; Cyclooxygenase 1; Cyclooxygenase 2; Diet; Fatty Acids; Fatty Acids, Omega-3; Flax; Intestinal Neoplasms; Intestine, Small; Lignans; Linseed Oil; Mice; Phytotherapy; Zea mays | 2009 |
Improved therapeutic efficacy against murine carcinoma by combining honokiol with gene therapy of PNAS-4, a novel pro-apoptotic gene.
PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit angiogenesis, and suppress tumor growth. In the present study, we investigated whether mouse PNAS-4 (mPNAS-4) could augment the apoptosis of tumor cells induced by honokiol in vitro, and whether the antiangiogenic activity of honokiol and induction of apoptosis by mPNAS-4 could work cooperatively to improve the antitumor efficacy in vivo. In vitro, mPNAS-4 inhibited proliferation of murine colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells induced by honokiol. Compared with treatment with mPNAS-4 or honokiol alone, in vivo systemic administration of an expression plasmid encoding mPNAS-4 and low-dose honokiol significantly suppressed tumor growth through the enhanced induction of apoptosis and the augmented inhibition of angiogenesis. Our data suggest that the combined treatment with mPNAS-4 plus honokiol augments antitumor effects in vitro and in vivo, and that the improved antitumor activity in vivo may be associated with enhanced induction of apoptosis and augmented inhibition of angiogenesis. The present study may provide a novel and effective method for the treatment of cancer. Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Biphenyl Compounds; Carcinoma, Lewis Lung; Cell Proliferation; Colonic Neoplasms; Combined Modality Therapy; Female; Genetic Therapy; Humans; In Situ Nick-End Labeling; Lignans; Liposomes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nitric Oxide Synthase; Tumor Cells, Cultured | 2009 |
Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM-p53 cascade in colon cancer cell lines.
The Mediterranean diet is rich in extra virgin olive oil (EVOO) and associated with a lower incidence of colorectal cancer. EVOO contains phenolic extracts with potential anticarcinogenic activity.. To assess the anticancer properties of EVOO phenolic extracts using in vitro models.. Phenolic profiles of two different EVOOs (A and B) were determined. RKO and HCT116 (both p53 proficient), SW480 (p53 mutant) and HCT116(p53-/-) (p53 knocked out) cell lines were treated with EVOO extracts and assessed for cell viability. Apoptosis was determined by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and changes in Bax transcript levels. Cell cycle analysis was determined by flow cytometry and western blots. To confirm the data, analysis of cell viability and cell cycle was performed with purified pinoresinol.. Chemical characterization showed that pinoresinol is the main phenol in EVOO-A, and oleocanthal predominates in EVOO-B. Only EVOO-A affected cell viability, which was significantly more pronounced in p53-proficient cells. At a concentration of 200 nM, p53-proficient cells showed increased apoptosis and G(2)/M arrest. In p53-proficient cells, ataxia telangiectasia mutated (ATM) and its downstream-controlled proteins were upregulated after treatment, with a parallel decrease of cyclin B/cdc2. Identical results on cell viability and cell cycle were obtained with purified pinoresinol, but this required a higher concentration than in EVOO-A.. Our results demonstrate that pinoresinol-rich EVOO extracts have potent chemopreventive properties and specifically upregulate the ATM-p53 cascade. This result was achieved at substantially lower concentrations in EVOO than with purified pinoresinol, indicating a possible synergic effect between the various polyphenols in olive oil. Topics: Anticarcinogenic Agents; Ataxia Telangiectasia Mutated Proteins; Blotting, Western; Cell Cycle Proteins; Cell Line, Tumor; Colonic Neoplasms; DNA-Binding Proteins; Flow Cytometry; Furans; Humans; In Situ Nick-End Labeling; Lignans; Olive Oil; Plant Oils; Protein Serine-Threonine Kinases; Tumor Suppressor Protein p53; Tumor Suppressor Proteins | 2008 |
Involvement of Ras/Raf-1/ERK actions in the magnolol-induced upregulation of p21 and cell-cycle arrest in colon cancer cells.
Previously, we showed that magnolol induces cell-cycle arrest in cultured colon and liver cancer cells through an upregulation of the p21 protein. The aim of this study was to delineate the molecular mechanism underlying this magnolol-induced increase of p21 protein. Thus our RT-PCR analysis demonstrated that the mRNA levels of p21 were increased at 1 h after magnolol treatment and sustained for at least 24 h. The p21 promoter activity was also increased by magnolol treatment. Western blot analysis demonstrated that treatment of COLO-205 cells with magnolol increased the levels of phosphorylation of extracellular signal-regulated kinase (ERK). Pretreatment of the cells with PD98059 abolished the magnolol-induced upregulation of p21 protein, suggesting the involvement of an ERK pathway in the magnolol-induced upregulation of p21 in COLO-205 cells. Ras inhibitor peptide abolished the magnolol-induced increase of phosphorylated ERK protein levels, increase of p21 protein, and decrease of thymidine incorporation. Moreover, treatment of COLO-205 with magnolol increased the phosphorylated Raf-1 protein (the Ras target molecule). Pretreatment of the cells with Raf-1 inhibitor reversed the magnolol-induced decrease in thymidine incorporation. Treatment of the cells with CaM kinase inhibitor, but not protein kinase A (PKA) inhibitor or phosphatidylinosital 3-kinase (PI3K) inhibitor, abolished the magnolol-induced activation of ERK and decrease of thymidine incorporation. Taken together, our results suggest that magnolol activates ERK phosphorylation through a Ras/Raf-1-mediated pathway. Subsequently, p21 expression is increased, and finally thymidine incorporation is decreased. Topics: Biphenyl Compounds; Cell Cycle; Cell Line, Tumor; Colonic Neoplasms; Extracellular Signal-Regulated MAP Kinases; Humans; Lignans; Nitric Oxide Synthase; Phosphorylation; Proto-Oncogene Proteins c-raf; Proto-Oncogene Proteins p21(ras); Signal Transduction; Up-Regulation | 2007 |
Chemopreventive effects of dietary flaxseed on colon tumor development.
Fatty acid composition of dietary fat plays a vital role in colon tumor development in animal models. Fats containing omega-6 fatty acids (e.g., corn oil) enhanced and omega-3 fatty acids (e.g., flaxseed oil) reduced chemically induced colon tumor development in rats. Lignans have also been shown to prevent colon tumor development in experimental animals. The objective of this investigation is to study the effects of dietary flaxseed meal, a source of both omega-3 fatty acid and lignans, on colon tumor development and compare them with the effects of dietary corn meal. Male Fischer rats, two groups of 24 each, were assigned to the AIN-93M diet supplemented with either 15% corn meal or 15% flaxseed meal, respectively. Carcinogenesis was initiated with subcutaneous injections of azoxymethane (15 mg/kg) once a week for 3 consecutive wk. After 35 wk of initiation, rats were anesthetized with ether. Blood was collected by cardiac puncture, and rats were sacrificed. The gastrointestinal tract was isolated. The site, size, and number of tumors were recorded. The fatty acid analysis of the collected serum and colon samples was performed. Expression of cyclooxygenase (COX)-1 and COX-2 was performed by Western blot method. Lignan levels in serum and colon samples were assayed. Colon tumor incidence, multiplicity, and size were found to be 82.6% and 29.4%; 1.3 and 0.3; and 44.4 and 5.3 mm(2) in corn and flaxseed meal groups, respectively. Colon and serum samples of the corn meal group showed higher levels of omega-6 fatty acid levels whereas the flaxseed meal group exhibited higher levels of omega-3 fatty acids. COX-1 and COX-2 expression in the flaxseed group was significantly lower (P < 0.05) as compared to the corn group. Dietary flaxseed meal containing high levels of omega-3 fatty acids and lignans is effective in preventing colon tumor development when compared with dietary corn meal possibly by increasing omega-3 fatty acid levels and decreasing COX-1 and COX-2 levels. Topics: Animals; Azoxymethane; Carcinogens; Colonic Neoplasms; Corn Oil; Cyclooxygenase 1; Cyclooxygenase 2; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Flax; Lignans; Male; Random Allocation; Rats; Rats, Inbred F344 | 2006 |
Lignans are involved in the antitumor activity of wheat bran in colon cancer SW480 cells.
Wheat bran was shown to provide protection against colorectal cancer in human intervention and animal studies. Our recent study showed, however, that antitumor activities of wheat bran from various wheat cultivars differed significantly even when wheat fiber was equal in diets. We hypothesized that phytochemical lignans in wheat bran may account for the differences among wheat cultivars in cancer prevention. The concentration of a major lignan, secoisolariciresinol diglycoside, was determined by HPLC in 4 selected wheat cultivars (i.e., Madison, Ernie, Betty, and Arapahoe). The lignan concentrations and their antitumor activities, previously determined in APC-Min mice, were correlated (r = 0.73, P < 0.02). The cancer preventive mechanisms of 2 prominent lignan metabolites (enterolactone and enterodiol) were further studied in human colonic cancer SW480 cells. Treatment with enterolactone and enterodiol, alone or in combination, at 0-40 micromol/L resulted in dose- and time-dependent decreases in cell numbers. Although the cytotoxicity as measured by trypan blue staining in adherent cells was not affected, DNA flow cytometric analysis indicated that the treatments induced cell cycle arrest at the S-phase. Western blot analysis for cyclin A, a required protein for S/G2 transition, showed that the cyclin A protein levels decreased after treatment with enterodiol or the combination of enterolactone and enterodiol at 40 micromol/L for 72 h. Apoptosis analysis by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay showed an increased percentage of apoptotic cells in the floating cells after enterodiol alone or combined treatments. These results suggest for the first time that lignans may contribute, at least in part, to the cancer prevention by wheat bran observed in APC-Min mice. Inhibition of cancer cell growth by lignan metabolites seems to be mediated by cytostatic and apoptotic mechanisms. Topics: Anticarcinogenic Agents; Cell Cycle; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Colonic Neoplasms; Dietary Fiber; Humans; Lignans; Phytotherapy; Triticum | 2005 |
Cytotoxic lignans from Larrea tridentata.
Six lignans, including the cyclolignan 3,4'-dihydroxy-3',4'-dimethoxy-6,7'-cyclolignan, were isolated from the flowering tops of Larrea tridentata. Additionally the flavanone, (S)-4',5-dihydroxy-7-methoxyflavanone, was isolated for the first time from L. tridentata or any member of the family Zygophyllaceae. All of the compounds were assessed for their growth inhibitory activity against human breast cancer, human colon cancer and human melanoma cell lines. The lignans had IC50 values of 5-60 microM with the linear butane-type lignans being the most potent, and it was found that colon cancer cells were the least sensitive cell type tested. The relative potency of linear butane type lignans against human breast cancer appears to correlate positively with the number of O-methyl groups present on the molecule. Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Colonic Neoplasms; Humans; Inhibitory Concentration 50; Larrea; Lignans; Melanoma; Molecular Structure | 2005 |
Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis.
Magnolol, a hydroxylated biphenyl compound isolated from the Chinese herb Hou p'u of Magnolia officinalis, has been reported to have anti-cancer activity. In the present study, magnolol at very low concentrations of 3-10 microM inhibited DNA synthesis and decreased cell number in cultured human cancer cells (COLO-205 and Hep-G2) in a dose-dependent manner, but not in human untransformed cells such as keratinocytes, fibroblasts, and human umbilical vein endothelial cells (HUVEC). Magnolol was not cytotoxic at these concentrations and this indicates that it may have an inhibitory effect on cell proliferation in the subcultured cancer cell lines. [(3)H] thymidine incorporation and flow cytometry analyses revealed that magnolol treatment decreased DNA synthesis and arrested the cells at the G0/G1 phase of the cell cycle. Moreover, the magnolol-induced cell cycle arrest occurred when the cyclin-CDK system was inhibited, just as p21 protein expression was augmented. When magnolol concentration was increased to 100 microM, apoptosis was observed in COLO-205 and Hep-G2 cells, but not in cultured human fibroblasts and HUVEC. COLO-205 cells implanted subcutaneously in nude mice formed solid tumors; subsequent daily i.p.-injections of magnolol led to profound regression of these tumors of up to 85%. In these tumors, an increase in the expression of p21 protein level and the occurrence of apoptosis were observed. These findings demonstrate for the first time that magnolol can inhibit the proliferation of tumor cells in vitro and in vivo. Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Calcium; Cell Cycle; Cell Cycle Proteins; Cell Division; Cell Nucleus; Cells, Cultured; Colonic Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; DNA; DNA Fragmentation; Humans; Kinetics; Lignans; Liver Neoplasms; Thymidine; Tumor Cells, Cultured | 2002 |
10-Demethoxystegane, a new lignan from Steganotaenia araliacea.
A new dibenzocyclooctadiene lactone lignan, 10-demethoxystegane (1), together with the known compounds steganone (2) and prestegane B (3), have been isolated from the organic extract of Steganotaenia araliacea(Apiaceae). Steganone (2) showed antiproliferative activity against an ovarian cancer cell line (OVCAR-3). Topics: 4-Butyrolactone; Antineoplastic Agents, Phytogenic; Apiaceae; Chromatography, High Pressure Liquid; Colonic Neoplasms; Female; Humans; Inhibitory Concentration 50; Lignans; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Tumor Cells, Cultured | 2001 |
Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells.
Magnolol has been reported to have anticancer activity. In this study we found that treatment with 100 microm magnolol induced apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines but not in human untransformed gingival fibroblasts and human umbilical vein endothelial cells. Our investigation of apoptosis in Hep G2 cells showed a sequence of associated intracellular events that included (a) increased cytosolic free Ca(2+); (b) increased translocation of cytochrome c (Cyto c) from mitochondria to cytosol; (c) activation of caspase 3, caspase 8, and caspase 9; and (d) downregulation of bcl-2 protein. Pretreatment of the cells with the phospholipase C inhibitor 1-[6-[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) or the intracellular chelator of Ca(2+) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM) inhibited the subsequent magnolol augmentation of [Ca(2+)](i) and also the activation of caspase-8 and caspase-9, so that the occurrence of apoptosis in those cells was greatly reduced. Pretreatment of the cells with ZB4 (which disrupts the Fas response mechanism) also decreased the subsequent magnolol-induced caspase-8 activation and reduced the occurrence of apoptosis. We interpreted these findings to indicate that the above-listed sequence of intracellular events led to the apoptosis seen in Hep G2 cells and that [Ca(2+)](i), Cyto c, and Fas function as intracellular signals to coordinate those events. Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Calcium; Caspases; Colonic Neoplasms; Cytochrome c Group; Endothelium, Vascular; fas Receptor; Fibroblasts; Humans; Lignans; Liver Neoplasms; Signal Transduction; Tumor Cells, Cultured | 2001 |
The influence of flaxseed and lignans on colon carcinogenesis and beta-glucuronidase activity.
Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk. This study determined whether over the long term flaxseed still exerts a colon cancer protective effect, whether its effect may, in part, be due to its high content of SD and whether any change in beta-glucuronidase activity plays a role in the protective effect. Six groups of male Sprague-Dawley rats were fed for 100 days either a basal high fat (20%) diet (BD), BD supplemented with 2.5 or 5% flaxseed or 2.5 or 5% defatted flaxseed (equivalent to the respective flaxseed diets) or BD with a daily gavage of 1.5 mg SD. All rats were injected with a single dose of azoxymethane (15 mg/kg body wt) 1 week prior to commencing the dietary treatments. Urinary lignan excretion, which is an indicator of mammalian lignan production, was significantly increased in the flaxseed and defatted flaxseed groups. The total activity of cecal beta-glucuronidase was significantly increased in a dose-dependent manner by the flaxseed and defatted flaxseed diet groups. Compared with the control the number of aberrant crypts per focus was significantly reduced in the distal colon of the treated rats. Four microadenomas and two polyps were observed in the control group, but not in the treated groups. The total activity of beta-glucuronidase was positively correlated with total urinary lignan excretion and negatively with the total number of aberrant crypts and the total number of aberrant crypt foci in the distal colon. There were no significant differences between the flaxseed and the corresponding defatted flaxseed groups. It is concluded that flaxseed has a colon cancer protective effect, that it is due, in part, to SD and that the protective effect of flaxseed is associated with increased beta-glucuronidase activity. Topics: Animals; Anticarcinogenic Agents; Body Weight; Butylene Glycols; Cecum; Colonic Neoplasms; Eating; Fatty Acids; Glucosides; Glucuronidase; Hydrogen-Ion Concentration; Lignans; Male; Organ Size; Plant Extracts; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Seeds | 1996 |
Just the flax, ma'am: researchers testing linseed.
Topics: Animals; Anticholesteremic Agents; Antineoplastic Agents; Cell Division; Colonic Neoplasms; Humans; Lignans; Linseed Oil; Plants, Edible; Seeds | 1994 |
Flaxseed supplementation and early markers of colon carcinogenesis.
Since flaxseed ingestion produces potentially anticarcinogenic lignans in the colon, this study determined whether flaxseed decreases the risk for colon carcinogenesis. Following a single injection of azoxymethane (15 mg/kg body wt.), five groups of male Sprague-Dawley rats were fed a high-fat (20% corn oil) basal diet with or without supplementation with 5% or 10% flaxseed meal (FM) or flaxseed flour (FF) for four weeks. Upon sacrifice, colons were examined for aberrant morphology and cell proliferation. In the descending colon of supplemented groups, the total number of aberrant crypts and foci were significantly reduced by 41-53% and 48-57%, respectively. The labeling index (LI) was also 10-22% lower in these groups, except for the 5% FM group. While these effects are not linearly related to the level of flaxseed fed, it suggests that flaxseed feeding may reduce the risk for colon carcinogenesis. Topics: Animals; Colon; Colonic Neoplasms; Dietary Fats; Food, Fortified; Lignans; Lignin; Male; Rats; Rats, Inbred Strains; Reference Values; Seeds | 1992 |
Does fiber-rich food containing animal lignan precursors protect against both colon and breast cancer? An extension of the "fiber hypothesis".
Topics: 4-Butyrolactone; Breast Neoplasms; Chemical Phenomena; Chemistry; Colonic Neoplasms; Dietary Fiber; Estrogens; Female; Humans; Lignans; Male; Plant Extracts | 1984 |