lignans and Ovarian-Neoplasms

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Diet, Vegetarian; Dietary Fats; Dietary Fiber; Endometrial Neoplasms; Estrogens; Estrogens, Non-Steroidal; Female; Gonadal Steroid Hormones; Humans; Incidence; Isoflavones; Lignans; Lignin; Male; Menopause; Ovarian Neoplasms; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Risk Factors

Phytoestrogens are plant-derived compounds that are structurally similar to endogenous estrogens. Studies have shown phytoestrogens to have possible health benefits although they could also act as endocrine disruptors. This is particularly relevant for estrogen-dependent cancers since estrogens increase risk of breast, endometrial, and ovarian cancer. Using data from the National Health and Nutritional Examination Survey (NHANES), we assessed the associations between urinary phytoestrogens (daidzein, equol, o-Desmethylangolensin (O-DMA), genistein, enterodiol, enterolactone) and breast, endometrial, and ovarian cancer using multivariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs). Cancer diagnosis and other characteristics were collected via in-person questionnaires. We found women in the highest tertile for daidzein and enterodiol had over twice the odds of having breast cancer (OR = 2.51, 95% CI 1.44-4.36 for daidzein, OR = 2.78, 95% CI 1.44-5.37 for enterodiol). In addition, women in the highest tertiles for daidzein and genistein had three to four times the odds of having endometrial cancer, respectively (OR = 3.09, 95% CI 1.01-9.49 for daidzein, OR = 4.00, 95% CI 1.38-11.59 for genistein). Overall, phytoestrogens were positively associated with breast and endometrial cancer although the associations varied by phytoestrogen type. Additional studies are needed to further inform phytoestrogens' role in disease etiology.Supplemental data for this article is available online at at https://doi.org/10.1080/01635581.2021.2020304.

Topics: Breast Neoplasms; Endometrial Neoplasms; Estrogens; Female; Genistein; Humans; Isoflavones; Lignans; Nutrition Surveys; Ovarian Neoplasms; Phytoestrogens

Gomisin A (GA) is an effective component of

Topics: Animals; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Proliferation; Complex Mixtures; Cyclin B1; Cyclin-Dependent Kinase 4; Cyclooctanes; Cysteine; Dioxoles; Eosine Yellowish-(YS); Female; Humans; Lignans; Mice; Ovarian Neoplasms; Oxidative Stress; Paclitaxel; Reactive Oxygen Species

Due to poor targeting ability of anti-tumor drugs and self-adaptation of tumors, the chemotherapy of ovarian cancer is still poorly effective. In recent years, the treatment of tumor with nano-targeted agents has become a potential research focus. In this study, a new type of short cell-penetrating peptide RPV-modified paclitaxel plus schisandrin B liposomes were constructed to disrupt VM channels, angiogenesis, proliferation and migration for the treatment of ovarian cancer.. In this study, clone assay, TUNEL, Transwell, wound-healing, CAM and mimics assay were used to detect the effects of RPV-modified liposomes on ovarian cancer SK-OV-3 cells before and after treatment. HE-staining, immunofluorescence and ELISA were used to further detect the expression of tumor-related proteins.. RPV-modified paclitaxel plus schisandrin B liposomes can inhibit angiogenesis, VM channel formation, invasion and proliferation of ovarian SK-OV-3 cells. In vitro and in vivo studies showed that tumor-related protein expression was down-regulated. Modification of RPV can prolong the retention time of liposome in vivo and accumulate in the tumor site, increasing the anti-tumor efficacy.. The RPV-modified paclitaxel plus schisandrin B liposomes have good anti-tumor effect, thus may provide a new avenue for the treatment of ovarian cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell-Penetrating Peptides; Cyclooctanes; Female; Humans; Lignans; Liposomes; Mice; Mice, Inbred BALB C; Ovarian Neoplasms; Paclitaxel; Polycyclic Compounds; Xenograft Model Antitumor Assays

Ovarian cancer is one of the highly prominent gynecological malignancies after breast cancer. Although myriad literature is available, there is no specific biomarker available for the personalized treatment strategy. The unavailability of effective drug therapy for ovarian cancer calls for an urgent push in its development from the multidisciplinary scientific community. Indian Ayurvedic medicine pharmacology is widely appreciated and accepted for its immense healthcare benefits. Bioinformatics and cheminformatics approaches can be effectively used to screen phytochemicals present in the Indian Ayurvedic plants against ovarian cancer target receptors. Recent studies discern that POTE, a cancer-testis antigen (CTA) family, plays a crucial role in the proliferation and progression of cancers including ovarian cancer. Specifically, POTEE paralog has been observed to be hypermethylated in ovarian cancer. This study undertakes an in silico analysis of Indian Ayurvedic plants for their anticancer efficacy against ovarian cancer proliferation target receptor POTEE. Structures of 100 phytochemicals from 11 Ayurvedic plants were screened with ADME criteria, and qualified phytochemicals were subjected to molecular docking and interaction analysis. Only 6 phytochemicals having a high affinity to the target receptor (POTEE) were then subjected to an all-atom replica exchange molecular dynamics simulation for 50 ns. Binding affinities of 6 phytochemicals cedeodarin, deodarin, hematoxylin, matairesinol, quercetin, and taxifolin with POTEE were -8.1, -7.7, -7.7, -7.9, -8.0, and - 7.7 kcal/mol, respectively, and their RMSD were recorded as zero. This study concludes that phytochemicals present in Indian Ayurvedic plants namely Cedrus deodara and Asparagus racemosus possess inhibitory effects against ovarian cancer proliferation receptor POTEE.

Topics: Antigens, Neoplasm; Cell Proliferation; Female; Furans; Hematoxylin; Humans; Lignans; Medicine, Ayurvedic; Molecular Docking Simulation; Ovarian Neoplasms; Phytochemicals; Quercetin

Ovarian cancer, one of the three leading malignancies in women, has high incidence and mortality worldwide. It is hard to diagnose until very late stages and the 5-year survival rate is very low, due mostly to its distant metastasis. Chemotherapy is currently the most common treatment to inhibit cancer growth, but long-term use could result in resistance and tumor recurrence in addition to damages to normal tissues and functions of the patients. In order to achieve safe and curative effects against cancers, many investigators have focused their attention on traditional Chinese herbal medicines. Paclitaxel, a natural antitumor agent, has significant effects on advanced malignancies including ovarian cancer and is in the standard front-line treatment. Additional natural anticancer substances have continually been discovered for their high effectiveness and low side-effects in ovarian cancer prevention and therapy. In this chapter, we summarize recent work on a selected group of natural components, including lignans, ellagic acid, luteolin, mangiferin, and Acanthopanax senticosus, which have all been demonstrated to reduce the progress of epithelial ovarian cancer in a dose-depend manner, by both in vitro and in vivo experiments. The mechanisms of the anticancer activities by these natural components involve expression suppression of MMP2 and MMP9.

Topics: Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Female; Humans; Lignans; Neoplasm Recurrence, Local; Ovarian Neoplasms

Topics: Animals; Apoptosis; Cell Proliferation; Cellular Senescence; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Lignans; Male; Mice; Mice, Nude; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Ovarian Neoplasms; Signal Transduction; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Honokiol, a natural biphenolic compound, exerts anticancer effects through a variety of mechanisms on multiple types of cancer with relatively low toxicity. Adenosine 5'‑phosphate‑activated protein kinase (AMPK), an essential regulator of cellular homeostasis, may control cancer progression. The present study aimed to investigate whether the anticancer activities of honokiol in ovarian cancer cells were mediated through the activation of AMPK. Honokiol decreased cell viability of 2 ovarian cancer cell lines, with an half‑maximal inhibitory concentration value of 48.71±11.31 µM for SKOV3 cells and 46.42±5.37 µM for Caov‑3 cells. Honokiol induced apoptosis via activation of caspase‑3, caspase‑7 and caspase‑9, and cleavage of poly‑(adenosine 5'‑diphosphate‑ribose) polymerase. Apoptosis induced by honokiol was weakened by compound C, an AMPK inhibitor, suggesting that honokiol‑induced apoptosis was dependent on the AMPK/mechanistic target of rapamycin signaling pathway. Additionally, honokiol inhibited the migration and invasion of ovarian cancer cells. The combined treatment of honokiol with compound C reversed the activities of honokiol in wound healing and Matrigel invasion assays. These results indicated that honokiol may have therapeutic potential in ovarian cancer by targeting AMPK activation.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Biphenyl Compounds; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Enzyme Activation; Female; Humans; Lignans; Mice; Models, Biological; Neoplasm Invasiveness; NIH 3T3 Cells; Ovarian Neoplasms; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Stem Cell Assay

Deoxyschizandrin, a major lignan of Schisandra berries, has been demonstrated to have various biological activities such as antioxidant, hepatoprotective, and antidiabetic effects. However, the anti-cancer effects of deoxyschizandrin are poorly characterized. In the present study, we investigated the anti-cancer effect of deoxyschizandrin on human ovarian cancer cell lines and tumour-associated macrophages (TAMs). Deoxyschizandrin induced G₀/G₁ phase cell cycle arrest and inhibited cyclin E expression in human ovarian cancer cells. Overexpression of cyclin E significantly reversed the deoxyschizandrin-induced cell growth inhibition. Interestingly, increased production of reactive oxygen species and decreased activation of Akt were observed in A2780 cells treated with deoxyschizandrin, and the antioxidant compromised the deoxyschizandrin-induced cell growth inhibition and Akt inactivation. Moreover, deoxyschizandrin-induced cell growth inhibition was markedly suppressed by Akt overexpression. In addition, deoxyschizandrin was found to inhibit the expression of the M2 phenotype markers CD163 and CD209 in TAMs, macrophages stimulated by the ovarian cancer cells. Moreover, expression and production of the tumour-promoting factors MMP-9, RANTES, and VEGF, which are highly enhanced in TAMs, was significantly suppressed by deoxyschizandrin treatment. Taken together, these data suggest that deoxyschizandrin exerts anti-cancer effects by inducing G₀/G₁ cell cycle arrest in ovarian cancer cells and reducing the protumoural phenotype of TAMs.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Chemokine CCL5; Cyclin E; Cyclooctanes; Female; Fruit; G1 Phase; Gene Expression Regulation, Neoplastic; Humans; Lignans; Macrophages; Matrix Metalloproteinase 9; Oncogene Proteins; Ovarian Neoplasms; Polycyclic Compounds; Reactive Oxygen Species; Schisandra; Vascular Endothelial Growth Factor A

To observe the growth inhibition of subcutaneous ovarian cancer xenografts in nude mice and mechanisms by ultrasound irradiation with honokiol-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) microbubbles (HK-PCEC-MB) as a promising therapeutic approach to ovarian tumor. HK-PCEC-MB were prepared using the double-emulsion solvent evaporation technique. Particles were characterized with regard to shape, size, distribution and surface potential using dynamic light scattering and the Malvern Zetasizer ZS90 system. Entrapment efficiency and loading amounts of honokiol were determined via high-performance liquid chromatography (HPLC). Pharmacological activity and optimal mode of action were examined using MTT assay. Nude mice were sorted into five groups of cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) ovarian cancer cell subcutaneous xenograft models: (1) HK-PCEC-MB+ultrasound; (2) HK; (3) PCEC-MB+ultrasound; (4) HK-PCEC-MB; (5) controls. We observed rates of growth inhibition, necrosis, and apoptosis, as well as microvessel density (MVD) changes. Physical properties of HK-PCEC-MB followed the normal pattern. The drug entrapment efficiency of HK-PCEC-MB was 65.08±2.31% and drug loading amount was 6.51±0.23%. Cancer cell survival rate was lowest in vitro at a drug concentration of 10 μg/mL with exposure to 2.58 W ultrasonic wave. In ultrasound irradiation combined with HK-PCEC-MB group, rates of necrosis and apoptosis were the highest, while the number of microvessel was the least. We have successfully prepared self-assembled HK-PCEC-MB that inhibits resistant human ovarian tumor growth by ultrasound irradiation.

Topics: Animals; Biphenyl Compounds; Female; Humans; Lignans; Mice; Mice, Nude; Microbubbles; Ovarian Neoplasms; Particle Size; Polyesters; Polyethylene Glycols; Ultrasonic Waves

Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented.. We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL.. The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development.. END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.

Topics: 4-Butyrolactone; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Survival; Female; Humans; Lignans; Mice, Inbred BALB C; Mice, Nude; Ovarian Neoplasms; Phytoestrogens; Tumor Burden; Wound Healing

The objective of the present study was to find the optimum dose of flaxseed that would decrease PG and alter oestrogen pathway endpoints implicated in ovarian cancer. In the study, four groups of fifty 1.5-year-old chickens were fed different amounts of flaxseed (0, 5, 10 or 15% of their total diet) for 4 months and were then killed to collect blood and tissues. Levels of flaxseed lignan metabolites, Enterolactone (EL) and Enterodiol (ED) were measured in the serum, liver and ovaries by liquid chromatography-MS/MS, and n-3 and n-6 fatty acid (FA) levels were measured by GC. The effects of the varied flaxseed doses were assessed by measuring levels of PGE2 and oestrogen metabolites (16-hydroxyestrone (16-OHE1) and 2-hydroxyestrone (2-OHE1)) as well as by analysing the expression of the oestradiol metabolising enzymes CYP3A4 (cytochrome p450, family 3, subfamily A, polypeptide 4), CYP1B1 (cytochrome p450, family 1, subfamily B, polypeptide 1) and CYP1A1 (cytochrome p450, family 1, subfamily A, polypeptide 1) and that of oestrogen receptor α (ERα) in the ovaries. The ratio of n-3:n-FA increased with an increase in flaxseed supplementation and corresponded to a dose-dependent decrease in cyclo-oxygenase-2 protein and PGE2 levels. EL and ED increased in the serum, liver and ovaries with increased concentrations of flaxseed. Flaxseed decreased the expression of ERα in the ovaries. The ratio of 2-OHE1:16-OHE1 in the serum increased significantly in the 15% flaxseed diet, and there was a corresponding increase in CYP1A1 in the liver and decrease in CYP3A4 in the ovaries. CYP1B1 mRNA also decreased with flaxseed diet in the ovaries. The 15% flaxseed-supplemented diet significantly decreased inflammatory PGE2, ERα, CYP3A4, CYP1B1 and 16-OHE1, but it increased CYP1A1 and 2-OHE1, which thus reduced the inflammatory and pro-carcinogenic micro-environment of the ovaries.

Topics: 4-Butyrolactone; Animals; Anticarcinogenic Agents; Chickens; Cyclooxygenase 1; Cyclooxygenase 2; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Cytochrome P-450 CYP3A; Diet; Dietary Supplements; Dinoprostone; Estrogen Receptor alpha; Estrogens; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Flax; Hydroxyestrones; Lignans; Liver; Ovarian Neoplasms; Ovary; RNA, Messenger

Phyto-oestrogens have been suggested to have a protective effect on hormone-sensitive cancers. However, few studies have investigated the association between dietary phyto-oestrogens and gynaecological cancers. In the present study, we analysed data from two population-based case-control studies of ovarian (1366 cases and 1414 controls) and endometrial (1288 cases and 1435 controls) cancers. Dietary intake information was obtained using a 135-item FFQ, and phyto-oestrogen intake was estimated using published food composition databases. Unconditional logistic regression was used to estimate adjusted OR and 95% CI. In multivariable analyses, there was a suggestive pattern of inverse associations between increasing intakes of total phyto-oestrogens, isoflavones and enterolignans and the risk of ovarian cancer. However, the results only reached statistical significance for the lignan compounds matairesinol and lariciresinol, where the OR for the highest v. the lowest intake category was 0.72 (95% CI 0.54, 0.96; P for trend = 0.02) for matairesinol and 0.72 (95% CI 0.55, 0.96; P for trend = 0.03) for lariciresinol. When the risk of ovarian cancer was assessed by subtype, there was an indication that increasing intakes of phyto-oestrogens may be associated with a decreased risk of mucinous (cases n 158) ovarian tumours (OR for the highest v. the lowest intake category: 0.47 (95% CI 0.24, 0.93); P for trend = 0.04). However, there were no significant associations with other histological subtypes. In contrast, dietary phyto-oestrogens (total or any subclass) were unrelated to the risk of endometrial cancer cases overall or by subtype.

Topics: Adenocarcinoma, Mucinous; Aged; Australia; Case-Control Studies; Diet; Diet Surveys; Endometrial Neoplasms; Female; Furans; Humans; Isoflavones; Lignans; Lignin; Logistic Models; Middle Aged; Odds Ratio; Ovarian Neoplasms; Phytoestrogens; Surveys and Questionnaires

Arctigenin is a biologically active lignan extracted from the seeds of Arctium lappa and shows anticancer activity against a variety of human cancers. The aim of this study was to determine the effects of arctigenin on ovarian cancer cell proliferation and survival and associated molecular mechanisms. Human ovarian cancer OVCAR3 and SKOV3 cells were treated with arctigenin, and cell proliferation and apoptosis were assessed. Western blot analysis was used to examine signal transducer and activator of transcription-3 (STAT3) phosphorylation and survivin and inducible nitric oxide synthase (iNOS) expression. The involvement of STAT3/survivin/iNOS/NO signalling in arctigenin action was checked. Arctigenin treatment resulted in a significant and dose-dependent inhibition of cell proliferation. Arctigenin-treated cells showed a 4-6 times increase in the percentage of apoptosis, compared with control cells. Pre-treatment with Ac-DEVD-CHO, a specific inhibitor of caspase-3, counteracted the induction of apoptosis by arctigenin. Arctigenin treatment significantly inhibited STAT3 phosphorylation and survivin and iNOS expression. Arctigenin-induced apoptosis was impaired by pre-transfection with survivin-expressing plasmid or addition of chemical nitric oxide (NO) donors. Additionally, exogenous NO prevented the suppression of STAT3 phosphorylation and survivin expression by arctigenin. Arctigenin treatment inhibits the proliferation and induces caspase-3-dependent apoptosis of ovarian cancer cells. Suppression of iNOS/NO/STAT3/survivin signalling is causally linked to the anticancer activity of arctigenin. Therefore, arctigenin may be applicable to anticancer therapy for ovarian cancer.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Caspase 3; Cell Line, Tumor; Female; Furans; Humans; Inhibitor of Apoptosis Proteins; Lignans; Nitric Oxide; Nitric Oxide Synthase Type II; Ovarian Neoplasms; Signal Transduction; STAT3 Transcription Factor; Survivin

Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol.

Topics: Biphenyl Compounds; Caspase 3; Cell Growth Processes; Cell Line, Tumor; Cell Transformation, Neoplastic; Cyclin D1; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Humans; Lignans; Neoplasm Metastasis; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-akt; Receptor, ErbB-2; Signal Transduction; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A

While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention.. We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol.. No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little evidence of an inverse association for isoflavones, lignans, or coumestrol.. This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance.

Topics: Adult; Carcinoma, Ovarian Epithelial; Case-Control Studies; Confidence Intervals; Coumestrol; Dietary Supplements; Female; Humans; Isoflavones; Lignans; Middle Aged; Neoplasms, Glandular and Epithelial; New Jersey; Odds Ratio; Ovarian Neoplasms; Phytoestrogens; Regression Analysis; Soy Foods; Women's Health

A study of an EtOH extract obtained from the roots of the Madagascan plant Terminalia tropophylla H. Perrier (Combretaceae) led to isolation of the oleanane-type triterpenoid saponin 1, the lignan derivative 2, and the two known saponins arjunglucoside I (3) and sericoside (4). The structures of compounds 1 (terminaliaside A) and 2 (4'-O-cinnamoyl cleomiscosin A) were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compound 1 showed antiproliferative activity against the A2780 human ovarian cancer cell line with an IC(50) value of 1.2 microM.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Ecosystem; Female; Humans; Inhibitory Concentration 50; Lignans; Madagascar; Molecular Structure; Oleanolic Acid; Ovarian Neoplasms; Phytotherapy; Plant Extracts; Plant Roots; Saponins; Terminalia; Triterpenes

Honokiol (HK) shows potential application in cancer treatment, but its poor water solubility restricts clinical application greatly. In this paper, monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) was synthesized by ring-opening polymerization and processed into nanoparticle for honokiol delivery. Chemical structure of the synthesized polymer was confirmed by (1)H NMR, and its molecular weight was determined by gel permeation chromatography (GPC). Honokiol loaded MPEG-PLA nanoparticles were prepared by solvent extract method. And particle size distribution, morphology, drug loading, drug release profile and anticancer activity in vitro were studied in detail. The described honokiol loaded MPEG-PLA nanoparticles in this paper might be a novel formulation for honokiol delivery.

Topics: Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemistry, Pharmaceutical; Chromatography, Gel; Dose-Response Relationship, Drug; Drug Carriers; Female; Hemolysis; Humans; Kinetics; Lignans; Magnetic Resonance Spectroscopy; Molecular Structure; Molecular Weight; Nanoparticles; Nanotechnology; Ovarian Neoplasms; Particle Size; Polyesters; Polyethylene Glycols; Solubility; Solvents; Surface Properties; Technology, Pharmaceutical

In this article, poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles were successfully prepared for honokiol delivery in vitro. Blank or honokiol loaded PCL-PEG-PCL nanoparticles were prepared in moderate condition by solvent diffusion method without using any surfactants. The prepared blank PCL-PEG-PCL nanoparticles are mono-dispersed and smaller than 200 nm. The particle size increased with increase in polymer concentration and oil-water (O/W) ratio. The prepared PCL-PEG-PCL nanoparticles (40 mg/mL, ca. 106 nm) did not induce hemolysis in vitro. And the 50% inhibiting concentration (IC50) of it (48 h) on HEK293 cells was higher than 5 mg/mL. Honokiol could be efficiently loaded into PCL-PEG-PCL nanoparticles and released from these nanoparticles in an extended period in vitro. After honokiol (HK) was entrapped into PCL-PEG-PCL nanoparticles, the particle size increased with the increase in HK/PCEC mass ratio in feed, and the encapsulated honokiol retained potent anticancer activity in vitro. The PCL-PEG-PCL nanoparticle was suitable for honokiol delivery, and such honokiol loaded PCL-PEG-PCL nanoparticle was a novel honokiol formulation.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cell Line; Cell Line, Tumor; Drug Carriers; Drugs, Chinese Herbal; Erythrocytes; Female; Hemolysis; Humans; Lignans; Nanoparticles; Ovarian Neoplasms; Particle Size; Polyesters; Polyethylene Glycols; Rabbits; Solvents

Honokiol has been receiving attention as an anticancer agent because of its anti-tumor effect. In the current study, we encapsulated honokiol with liposome and tested it on cisplatin-sensitive (A2780s) and -resistant (A2780cp) human ovarian cancer models.. The anti-tumor activity of liposomal honokiol (Lipo-HNK) was evaluated in nude mice bearing A2780s and A2780cp s.c. tumors. Mice were treated twice weekly with i.v. administration of Lipo-HNK (10 mg/kg), control liposome (10 mg/kg), 0.9% NaCl solution or weekly with intraperitoneally administered cisplatin (5 mg/kg) for 3 weeks. Tumor volume and survival time were observed. Assessment of apoptotic cells by TUNEL assay was conducted in tumor tissue. Microvessel density within tumor tissue was determined by CD34 immunohistochemistry. For in vitro study, induction of apoptosis by Lipo-HNK was examined by PI staining fluorescence microscopy, DNA fragmentation assay and flow cytometric analysis.. Administration of Lipo-HNK resulted in significant inhibition (84-88% maximum inhibition relative to controls) in the growth of A2780s and A2780cp tumor xenografts and prolonged the survival of the treated mice. These anti-tumor responses were associated with marked increases in tumor apoptosis, and reductions in intratumoral microvessel density.. The present findings suggest that Lipo-HNK may provide an effective approach to inhibit tumor growth in both cisplatin sensitive and -resistant human ovarian cancer with minimal side effects.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cell Line, Tumor; Cisplatin; Drug Resistance, Neoplasm; Female; Humans; Immunohistochemistry; Lignans; Liposomes; Mice; Mice, Nude; Ovarian Neoplasms

To observe the anti-tumor activities of honokiol on human ovarian tumor in vitro and in vivo.. Cells were treated with honokiol, and the effects on proliferation and apoptosis were examined by MTT, DNA ladder, Hoechst staining, and flow cytometry assays. Expression of Bcl-2 members and caspase-3 were assessed. Measurements of tumor volume and microvessel densities (MVDs) were performed.. Honokiol significantly inhibited proliferation and induced apoptosis, with alteration of Bcl-2 members and caspase-3. Administration of honokiol to tumor-bearing animals decreased MVD and resulted in inhibition of tumor growth.. Honokiol could induce apoptosis and inhibit angiogenesis in vitro and in vivo, suggesting a novel and attractive therapeutic candidate for ovarian tumor treatment.

Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Biphenyl Compounds; Cell Line, Tumor; Disease Models, Animal; Female; Humans; Lignans; Mice; Mice, Nude; Neovascularization, Pathologic; Ovarian Neoplasms

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