Effects of phytoestrogens on aromatase, 3 beta and 17 beta-hydroxysteroid dehydrogenase activities and human breast cancer cells

Isoflavones and others phytoestrogens have been suggested to be anticarcino genic. Anti-aromatase, antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there i s a reduced incidence of breast cancer associated with diet. In this study, we explored some mechanisms by which they can exert cancer-preventive effe cts. Phytoestrogens were tested for estimating anti-aromatase, anti-3 beta- hydroxysteroid dehydrogenase Delta(5)/Delta(4) isomerase (3 beta-HSD) and a nti-17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activities in human placental microsomes, We found that isoflavonoids and compounds which prese nted the phenolic B ring in the 3 position on the pyran ring preferentially inhibited SP-HSD and/or 17 beta-HSD activities than aromatase activity. We also evaluated their interactions with the estrogen receptor using a stabl y transfected human breast cancer cell line (MVLN). On the other hand phyto estrogens were evaluated for their effects on the proliferation in estrogen -dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. W e established a relationship structure-activity and determined regions or/a nd substituents essential for these different activities. However, at high concentrations it seems that some phytoestrogens exert their protection aga inst breast cancer through other estrogen-independent mechanisms.