Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids.
The interaction between the estrogen receptor and a variety of flavonoids was studied in the presence or absence of estradiol using a stably-transfected human breast cancer cell line (MVLN). On the other hand, flavonoids were evaluated for their effects on proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions and/or substituents essential for estrogenic or antiestrogenic activities. In contrast, we did not find the same relationship for cell proliferation. Among all flavonoids used, only 7-methoxyflavanone and 7,8-dihydroxyflavone at high concentrations (50 microM) possess antiestrogenic and antiproliferative activities. These results suggest that two hydroxyls (in positions 7 and 8) or 7-methoxy substituents are essential for the antiestrogenic activity of flavonoids. However, it seems that flavonoids at high concentrations exert their antiproliferative activity through other estrogen receptor-independent mechanisms.
Le Bail
J C
JC
UPRES EA 1085, Laboratoire de Biochimie, Faculté de Pharmacie, Limoges, France.
Varnat
F
F
Nicolas
J C
JC
Habrioux
G
G
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D017930:Genes, Reporter / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008156:Luciferases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D005419:Flavonoids; D044948:Flavonols; D011960:Receptors, Estrogen; D013629:Tamoxifen; D019833:Genistein; D008156:Luciferases