Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells.
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.
Le Bail
J C
JC
UPRES EA 1085 Biomolécules et cibles cellulaires tumorales-Prolifération cellulaire et inhibition enzymatique, Laboratoire de Biochimie, Limoges, France.
Champavier
Y
Y
Chulia
A J
AJ
Habrioux
G
G
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology; D047072:Aromatase Inhibitors; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D007887:Fabaceae / Q000737:chemistry; D006801:Humans; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D048789:Phytoestrogens; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D028321:Plant Preparations; D010946:Plants, Medicinal; D036343:Pterocarpans; D014407:Tumor Cells, Cultured; D000094162:Phytoalexins
D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047072:Aromatase Inhibitors; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D008156:Luciferases; D048789:Phytoestrogens; D028321:Plant Preparations; D036343:Pterocarpans; C406425:sativan; C047353:medicarpin; D000094162:Phytoalexins