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Phytoestrogens, Coumestrol , Resveratrol, and Xenoestrogens Interactions With Cancer. By Michaela Phillips. Introduction. Cancer is a major cause of mortality

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phytoestrogens coumestrol resveratrol and xenoestrogens interactions with cancer

Phytoestrogens, Coumestrol, Resveratrol, and Xenoestrogens Interactions With Cancer

By Michaela Phillips

introduction
Introduction
  • Cancer is a major cause of mortality
  • National Cancer Institute 2011-2012 Cancer Trends Report shows prostate, breast, lung, and colorectal cancer rates are decreasing compared to other cancers
  • Use of phytoestrogens and estrogenic compounds
estrogen metabolism
Estrogen Metabolism
  • Estradiol conversion to estrone and estriol
  • Products oxidized by Cyt P450 and hydroxillated at -2, -4, -16
    • CYP1B1: Enzyme that catalyzes at -16 position
    • CYP1A1: Enzyme that catalyzes at -2 position
      • Inducible by diet including cruciferous vegetables, EFAs, flax and soy (controversial)

Lord & Bongiovanni, 2001, p115

estrogen metabolism1
Estrogen Metabolism
  • -2/-16 ratio – Higher ratio is desirable to reduce risk

Lord & Bongiovanni, 2001, p123

pytoestrogens and ovarian cancer
Pytoestrogens and Ovarian Cancer
  • 10% inherited through genes
  • Bandera et Al study on phytoestrogen effects on epithelial ovarian cancer
    • 205 cases from 6 NJ counties from the state cancer registry; 390 controls
    • Modified Block food frequency questionnaire
      • Lignans (flax, grain/bread, nuts, coffee, tea, FV) found to be major source of phytoestrogens in this population.
    • Results:
      • OR for highest vs. lowest tertile of lignan intake = 1.0, 95% CI: 0.68-1.79
      • OR of 0.66 for the highest tertile (CI of 95%: 0.41-1.08)
phytoestrogens and prostate cancer
Phytoestrogens and Prostate Cancer
  • Leading cause of death in males
  • Soy phytoestrogens
    • Daidzen and genistein
      • Reversal of hypermethyllation of BRCA1, EPHB2, and GSTP1 in DU-145 and PC-3 cell lines (prostate cancer)
    • Genistein
      • Slightly upregulated proteins for BRCA1, EPHB2, and GSTP1 possibly due to longer exposure to treatment
phytoestrogens and breast cancer
Phytoestrogens and Breast Cancer
  • Soy Isoflavones
    • American Cancer Society advises breast cancer survivors to limit soy intake
    • Sakamoto study
      • Soy phytoestrogens moderately increased cancer cell growth in the presence of E2 (17-estradiol)
      • Daidzen and Genistein
        • Did not reduce tumor activity
        • Slightly suppressed E2
      • Genistein: Induced apoptosis and reduced BC1-2/Bax ratio.
      • Glycitein: Repressed cell growth, induced apoptosis, and slightly reduced BC1-2/Bax ratio. Showed a weak effect on transactivation of estrogen receptors compared with other isoflavones.
resveratrol
Resveratrol
  • Sakamoto et Al. (2009)
    • Resveratrol inhibited E2
    • Resveratrol showed the greatest antitumor effect whether or not E2 was present
    • Results were similar at high or low serum doses
    • Shows promise for future research
coumestrol
Coumestrol
  • Found in alfalfa, red clover, legumes, and soy products
  • Coumestrolstimulates tumor growth, but is found in such low concentrations in food that it is unlikely to increase the risk of developing breast cancer (Sakamoto et Al. 2009)
xenoestrogens
Xenoestrogens
  • Chemicals that have estrogenic properties such as Bisphenol A (BPA) that can leach out of plastic when heat is applied
  • July 2013, the FDA banned the use of BPA in infant formula packaging due to market abandonment, not safety
  • Fernandez and Russo (2010)
    • BisphenolA could be involved in the initiation or progression of breast cancer
  • Lord and Bongiovanni (2011)
    • Limiting xenoestrogen exposure lowers cancer risk possibly by reducing 16hydroxyllation
conclusion
Conclusion
  • Higher -2/-16 ratio
  • Diet manipulation can increase -2-OHE
    • Consumption of cruciferous vegetables, flax, EFA
  • Soy Isoflavones
    • Reversed DNA methyllation in prostate cancer cell lines
    • Did not reduce tumor activity in breast cancer cells
  • Glycitein: Beneficial to inhibit tumor growth and apoptosis, but weak estrogen receptor transactivity.
  • Resveratrol:
    • Promising potential
    • Effective at high or normal doses independent of E2
  • Xenoestrogens: Avoid exposure
slide12

References

Adjaklyet Al., M., Bosviel, R., Rabiau, N., Boiteux, J. P., Bignon, Y. J., Guy, L., & Bernard-Gallon, D. (2011). DNA methylation and soy phytoestrogens: quantitative study in DU-145 and PC-3 human prostate cancer cell lines. Epigenomics, 3 (6), 795-803.

American Cancer Society, Guidelines On Nutrition and Physical Activity for Cancer Prevention, retrieved in October 2013 from: http://www.cancer.org/healthy/eathealthygetactive/acsguidelinesonnutritionphysicalactivityforcancerprevention/acs-guidelines-on-nutrition-and-physical-activity-for-cancer-prevention-dietand-activity

Bandera, E., King, M., Chandran, U., Paddock, L., Rodriguez-Rodriguez, L., & Olson, S. (2011). Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study. BMC women's health, 11(1), 40.

Cancer Trends Progress Report – 2011/2012 Update, National Cancer Institute, NIH, DHHS, Bethesda, MD, August 2012, http://progressreport.cancer.gov.

Cotterchio M, Boucher BA, Kreiger N, Mills CA, Thompson LU (2008): Dietary phytoestrogen intake-lignans and isoflavones-and breast cancer risk (Canada). Cancer Causes Control, 19(3), 259-272.

European Food Safety Authority, Bisphenol A ban, retrieved on 1 Dec 2013 from: http://www.efsa.europa.eu/en/topics/topic/bisphenol.htm

Fernandez, S. V., & Russo, J. (2010). Estrogen and xenoestrogens in breast cancer. Toxicologic pathology, 38(1), 110-122.

Lord, R. S., Bongiovanni, B., & Bralley, J. A. (2002). Estrogen metabolism and the diet-cancer connection: rationale for assessing the ratio of urinary hydroxylated estrogen metabolites. Alternative Medicine Review, 7(2), 112-129.

Sakamoto et Al., T., Horiguchi, H., Oguma, E., & Kayama, F. (2010). Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. The Journal of Nutritional Biochemistry,21(9), 856-864.

Shu, X. O., Zheng, Y., Cai, H., Gu, K., Chen, Z., Zheng, W., & Lu, W. (2009). Soy food intake and breast cancer survival. JAMA: the journal of the American Medical Association, 302(22), 2437-2443.

Thompson, L. U., Boucher, B. A., Liu, Z., Cotterchio, M., & Kreiger, N. (2006). Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan. Nutrition and cancer, 54(2), 184-201.

US Food and Drug Administration, Center for Food Safety and Applied Nutrition (CFSAN, 2013), FDA Regulations No Longer Authorize the Use of BPA in Infant Formula Packaging Based on Abandonment; Decision Not Based on Safety, retrieved on 1 December 2013 from: http://www.fda.gov/food/newsevents/constituentupdates/ucm360147.htm