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Phytoestrogens, Coumestrol,
Resveratrol, and Xenoestrogens
Interactions With Cancer
By Michaela Phillips
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
• 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 Metabolism
• -2/-16 ratio –
Higher ratio is
desirable to reduce
risk
Lord & Bongiovanni, 2001, p123
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
• 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
• 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
• 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
• Found in alfalfa, red clover, legumes, and soy
products
• Coumestrol stimulates 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
• 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)
– Bisphenol A 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
• 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
References
Adjakly et 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-andphysical-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