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Flavonoids and steroid hormone-dependent cancers

Posted on:2002-01-03Degree:Ph.DType:Dissertation
University:University of Toronto (Canada)Candidate:Rosenberg Zand, Rachel StaceyFull Text:PDF
GTID:1464390011493480Subject:Health Sciences
Abstract/Summary:
Steroid hormone-dependent cancers, including breast and prostate, are leading causes of cancer morbidity and mortality in North America. In Asian countries, these diseases are much less common. Nutritional and lifestyle factors are associated with differences in incidence, with an emphasis on consumption of plant foods, in particular soy. Flavonoids are one class of compounds present in these plant foods. With over 4000 identified members, these compounds have been hypothesized to have several important chemopreventive effects.; The purpose of this project was to assess the steroid hormone activities of plant foods, with a reference to soy, in three forms: pure flavonoids, plant extract (nutracetical), and whole (functional) food. After developing an in vitro bioassay, soy isoflavones and other flavonoids were evaluated for steroid hormone activities, defined as their ability to induce or inhibit production of estrogen- (pS2) and androgen/progestin- (prostate-specific antigen, PSA) regulated proteins. Genistein and biochanin A demonstrated highest estrogenic activity of the compounds tested, which was dose-response down to 10 −8 M and 10−7 M, respectively. These soy isoflavones also demonstrated significant anti-androgen activity (76% and 98%, respectively at 10−5 M).; Natural products and nutraceticals were then tested for steroid hormone activities. As with pure isoflavones, the commercial soy and red clover extracts had high estrogenic activity. Soy extract demonstrated 63% anti-androgen activity at the highest strength tested.; Finally, we determined the steroid hormone potentials of one functional food, soy, in healthy subjects. By using biological fluids obtained from individuals in a soy feeding study, we found that short-term feeding did not increase agonist potentials. Moreover, non-significant reductions in estrogenic and androgenic activities in women and men, respectively, may indicate that long-term feeding of this functional food may reduce risk factors for steroid-hormone dependent cancers.; These results indicate that soy isoflavones and other flavonoids have steroid hormone activities. These activities may act in vivo to modulate activities of potentially carcinogenic endogenous hormones. Further research is needed to determine the physiological importance of flavonoids in prevention and/or management of hormone-dependent cancers, and how to make best use of natural products, nutraceticals and functional foods in individuals at risk.
Keywords/Search Tags:Steroid hormone, Cancers, Flavonoids, Soy, Foods, Functional
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