Repressive effect of the phytoestrogen genistein on estradiol-induced uterine leiomyoma cell proliferation.
OBJECTIVE
Uterine leiomyomas are the most common gynecological benign tumor and greatly affect reproductive health and well-being. They are the predominant indication for hysterectomy in premenopausal women. Current epidemiological study reported that soy products intake is inversely associated with diseases leading to hysterectomy. Genistein is a soy-derived phytoestrogen and its inhibitory effect on leiomyoma cell proliferation is reported. In this study, we investigated the siginificant inhibitory effect of genistein on estradiol (E(2))-induced leiomyoma cells proliferation.


METHODS
The Eker rat-derived uterine leiomyoma cell line ELT-3 cells were used. Cell proliferation was assessed by counting the number of cells. The expression of estrogen receptors and peroxisome proliferator-activated receptor-gamma (PPARgamma) was evaluated by Western blot analysis.


RESULTS
PPARgamma was expressed in ELT-3 cells and genistein acted as PPARgamma ligand. This inhibitory effect of genistein was attenuated by the treatment of cells with PPARgamma antagonist bisphenol A diglycidyl ether (BADGE) or GW9662.


CONCLUSIONS
These experimental findings in vitro show that the repressive effect of genistein on E(2)-induced ELT-3 cell proliferation is through the activation of PPARgamma. Genistein may be useful as an alternative therapy for leiomyoma.
Miyake
Asako
A
Center for Asian Traditional Medicine, Tohoku University Graduate School of Medicine, Aoba, Sendai 980-8574, Japan.
Takeda
Takashi
T
Isobe
Aki
A
Wakabayashi
Atsuko
A
Nishimoto
Fumihito
F
Morishige
Ken-Ichirou
K
Sakata
Masahiro
M
Kimura
Tadashi
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol; D005260:Female; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D007889:Leiomyoma / Q000188:drug therapy*; D008024:Ligands; D047495:PPAR gamma / Q000378:metabolism; D048789:Phytoestrogens / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy*
D008024:Ligands; D047495:PPAR gamma; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D004958:Estradiol; D019833:Genistein