phytoestrogens and medicarpin

Isoflavones and others phytoestrogens have been suggested to be anticarcinogenic. Anti-aromatase, antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there is a reduced incidence of breast cancer associated with diet. In this study, we explored some mechanisms by which they can exert cancer-preventive effects. Phytoestrogens were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. We found that isoflavonoids and compounds which presented the phenolic B ring in the 3 position on the pyran ring preferentially inhibited 3beta-HSD and/or 17beta-HSD activities than aromatase activity. We also evaluated their interactions with the estrogen receptor using a stably transfected human breast cancer cell line (MVLN). On the other hand phytoestrogens were evaluated for their effects on the proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions or/and substituents essential for these different activities. However, at high concentrations it seems that some phytoestrogens exert their protection against breast cancer through other estrogen-independent mechanisms.

Topics: 17-Hydroxysteroid Dehydrogenases; 3-Hydroxysteroid Dehydrogenases; Anti-Inflammatory Agents, Non-Steroidal; Aromatase Inhibitors; Benzopyrans; Breast Neoplasms; Cell Division; Cells, Cultured; Enzyme Inhibitors; Estrogen Antagonists; Estrogens, Non-Steroidal; Fabaceae; Humans; Isoflavones; Luciferases; Magnetic Resonance Spectroscopy; Microsomes; Phytoestrogens; Placenta; Plant Preparations; Plants, Medicinal; Pterocarpans; Tumor Cells, Cultured