Whole flaxseed diet alters estrogen metabolism to promote 2-methoxtestradiol-induced apoptosis in hen ovarian cancer.

The study reported here demonstrates that a flaxseed-supplemented diet causes ovarian tumors in the laying hen to undergo apoptosis, resulting in a reduction of tumor burden, reducing the frequency and severity of ovarian cancer. We have previously shown in normal ovaries that flaxseed and its components down-regulate ERalpha and alter the expression of enzymes that metabolize estrogen. In this study, we analyzed the effects of the two main components of whole flaxseed, ligan and omega 3 fatty acids on estrogen metabolism and the estrogen receptor in ovarian tumors. ER alpha expression was up-regulated in the ovarian tumors and was not affected by diet. Liver CYP1A1 expression was significantly increased by the whole flaxseed diet with a corresponding increase in 2-methoxyestradiol plasma levels. We also observed increased p38 and ERK 1/2 MAPK activation in the ovary as well as an increase in apoptosis in the tumor epithelium. SMAD 7, a factor involved in the 2-methoxyestradiol-mediated apoptosis pathway was also up-regulated in tumors from the whole flaxseed diet group. 2-methoxyestradiol-induced antitumor effects were further validated by in human ovarian cancer cells. This study details the effect of flaxseed diet on estrogen metabolism and demonstrates the antiovarian cancer effects of 2-methoxyestradiol.

Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer.

PROBLEM: Ovarian cancer (OVCA) disseminates in a distinct pattern through peritoneal metastasis and little is known about the immunosuppression in the tumor microenvironment. Our goal was to determine changes in NK cell population during OVCA development and the effects of Ashwagandha (Withania somnifera, Dunal) supplementation on NK cell localization in laying hens with OVCA. METHODS: Frequency of NK cells in ovarian tumors at early and late stages in 3- to 4-year-old hens (exploratory study) as well as in hens supplemented with dietary Ashwagandha root powder for 90 days (prospective study) was examined. RESULTS: The population of stromal NK cells but not the intratumoral NK cells increased with OVCA development and progression. Ashwagandha supplementation decreased the incidence and progression of OVCA. Both the stromal and intratumoral NK cell population increased significantly (P < 0.0001) in Ashwagandha supplementated hens. CONCLUSION: The results of this study suggest that the population of stromal and tumorinfiltrating NK cells is increased by dietary Ashwagandha supplementation. Thus, Ashwagandha may enhance antitumor function of NK cells. This study may be useful for a clinical study to determine the effects of dietary Ashwagandha on NK cell immune function in patients with ovarian cancer.

A randomized parallel-group dietary study for stages II-IV ovarian cancer survivors.

OBJECTIVE: Few studies have examined the dietary habits of ovarian cancer survivors. Therefore, we conducted a study to assess the feasibility and impact of two dietary interventions for ovarian cancer survivors. METHODS: In this randomized, parallel-group study, 51 women (mean age, 53 years) diagnosed with stages II-IV ovarian cancer were recruited and randomly assigned to a low fat, high fiber (LFHF) diet or a modified National Cancer Institute diet supplemented with a soy-based beverage and encapsulated fruit and vegetable juice concentrates (FVJCs). Changes in clinical measures, serum carotenoid and tocopherol levels, dietary intake, anthropometry, and health-related quality of life (HRQOL) were assessed with paired t-tests. RESULTS: The recruitment rate was 25%, and the retention rate was 75% at 6 months. At baseline, 28% and 45% of women met guidelines for intake of fiber and of fruits and vegetables, respectively. After 6 months, total serum carotenoid levels and α- and ß-carotene concentrations were significantly increased in both groups (P<0.01); however, ß-carotene concentrations were increased more in the FVJC group. Serum ß-cryptoxanthin levels, fiber intake (+5.2g/day), and daily servings of juice (+0.9 servings/day) and vegetables (+1.3 servings/day) were all significantly increased in the LFHF group (all P<0.05). Serum levels of albumin, lutein and zeaxanthin, retinol, and retinyl palmitate were significantly increased in the FVJC group (all P<0.05). No changes in cancer antigen-125, anthropometry, or HRQOL were observed. CONCLUSION: Overall, this study supports the feasibility of designing dietary interventions for stages II-IV ovarian cancer survivors and provides preliminary evidence that a low fat high fiber diet and a diet supplemented with encapsulated FVJC may increase phytonutrients in ovarian cancer survivors.

Dietary phytoestrogens and the risk of ovarian cancer in the women's lifestyle and health cohort study.

BACKGROUND: Dietary intake of phytoestrogens has been inversely associated to hormone-dependent cancers, such as prostate and breast cancers. Few studies have investigated the association between ovarian cancer and intake of phytoestrogens. We evaluated the associations between intake of phytoestrogens (isoflavonoids/lignans/coumestrol) and fiber (vegetable/cereal) and risk of ovarian cancer. METHODS: In 1991-1992 a prospective population-based cohort study among Swedish women was conducted, including 47,140 women with complete dietary questionnaire data. During follow-up until December 2007, 163 women developed invasive (n = 117) and borderline (n = 46) ovarian cancers. The median follow-up time was 16 years and total person year was 747,178. Cox proportional hazards models were conducted to estimate multivariate risk ratios, 95% CI for associations with risk of ovarian cancer. RESULTS: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. In addition, we found no statistically significant association between intake of specific food items rich in phytoestrogens (berries, nuts, beans/soy, and crisp or whole-grain bread) and ovarian cancer risk overall. Fiber and coumestrol was inversely associated with borderline ovarian cancer, but not with invasive ovarian cancer. CONCLUSIONS: We found no association between intake of phytoestrogens or fiber and overall ovarian cancer risk. IMPACT: Phytoestrogens do not play a major etiologic role in ovarian cancer, at least among women in this Swedish cohort with low bean/soy intake. However, our results of a difference in the effect of fiber or coumestrol between invasive and borderline ovarian cancer need to be evaluated in larger studies.

Decreased severity of ovarian cancer and increased survival in hens fed a flaxseed-enriched diet for 1 year.

OBJECTIVE: With the exception of the laying hen, no other animal model of spontaneous ovarian surface epithelial cancer replicates the human disease. Flaxseed is the richest vegetable source of omega-3 fatty acids, which are chemopreventive in breast cancer and may be important in other cancers. The objective of this study was to determine if a flaxseed-enriched diet had a chemopreventive effect on ovarian cancer in the laying hen. METHODS: White Leghorn hens were fed with 10% flaxseed-enriched or standard diet for 1 year. The incidence and severity of ovarian cancer were determined by gross pathology and histology in the two groups. General health markers were also measured. Eggs were collected and analyzed by gas chromatography to determine omega-3 fatty acid levels. RESULTS: A significant reduction in late stage ovarian tumors was detected in the flaxseed-fed hens. Incidence rates of ovarian cancer were not significantly different between the two groups. The results indicate that a flaxseed diet increases overall survival in the laying hen. Flaxseed-fed hens' eggs incorporated significantly more omega-3 fatty acids compared to control hens. CONCLUSIONS: These findings show that 10% flaxseed supplementation for 1 year in the laying hen results in a significant reduction in the severity of ovarian cancer, but no change in the incidence of the disease. Hens fed flaxseed had overall better health and reduced mortality. These findings may provide the basis for a clinical trial that evaluates the efficacy of flaxseed as a chemosuppressant of ovarian cancer in women.

Effects of omega-3 fatty acids on components of the transforming growth factor beta-1 pathway: implication for dietary modification and prevention in ovarian cancer.

OBJECTIVE: We previously demonstrated that omega-3 fatty acids (OM-3FAs) have definitive inhibitory effects on ovarian cancer cell lines. We sought to determine whether the inhibitory effects of OM-3FAs were mediated by the transforming growth factor (TGF)-beta1 signaling pathway. STUDY DESIGN: Ovarian cancer cell lines were grown at 37 degrees C in 5% CO(2) and treated with OM-3FAs, omega-6 fatty acids, and control at different concentrations for 24-72 hours. Enzyme-linked immunosorbent assay (ELISA) assay and Western blot analysis were used to measure TGF-beta1, phosphorylated mothers against decapentaplegic (Smad)-3 and p21 protein levels. RESULTS: An ELISA assay demonstrated that OM-3FA treatment increased TGF-beta1 in all 3 Hey cell lines (P < .05). In both SKOV-3 and OVCAR-3 cells, TGF-beta1 levels were not significantly increased. Western blots confirmed increases in TGF-beta1, Smad-3 and p21 protein levels in Hey and HeyC2 but not SKOV-3 and OVCAR-3 cells. CONCLUSION: OM-3FAs increased the level of TGF-beta1, Smad-3, and p21 protein in ovarian cancer cells known to be more sensitive to their inhibitory effect.

Different quantities of two commercial liquid diets consumed by weight-losing cancer patients.

Twenty ambulatory, weight-losing patients with advanced cancer of the lung, breast, or ovary were randomized to supplement their diet for 2 months with either of two commercial complete liquid diets, one containing intact milk proteins and the other partially hydrolyzed soy proteins. Both products were prescribed as sip feeds in addition to normal food. The patients consumed more of the hydrolysate-containing product than of that with intact (milk) protein. The difference was significant and was maintained during both months of the study. An increase in total energy and protein was obtained in both groups, but was significant only with the hydrolysate product. At the end of the study there was no group difference in measures of nutritional status, but weight loss was halted in both groups.