期刊
LIFE SCIENCES
卷 66, 期 14, 页码 1281-1291出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0024-3205(00)00435-5
关键词
aromatase; 17 beta-hydroxysteroid dehydrogenase; 3 beta-hydroxysteroid dehydrogenase Delta(5)/Delta(4) isomerase; estrogen receptor; phytoestrogens; Galega officinalis
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-3 beta-hydroxysteroid dehydrogenase Delta(5)/Delta(4) isomerase (3 beta-HSD) and anti-17 beta-hydroxysteroid dehydrogenase (17 beta-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 SP-HSD and/or 17 beta-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.
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