Genistein in the presence of 17beta-estradiol inhibits proliferation of ERbeta breast cancer cells.
OBJECTIVE
Genistein, a soy component, has been shown to have a biphasic proliferative effect in breast cancer cells, inhibiting in vitro cell proliferation at high concentrations (>10 micromol/l), while stimulating cell proliferation at lower concentrations (<10 micromol/l). However, epidemiological studies have shown an inverse correlation between the intake of genistein and the incidence of breast cancer. One of the possible reasons for this discrepancy could be the differing status of the estrogen receptor (ERalpha and/or ERbeta). Genistein selectively binds to ERbeta with strong affinity and thereby could be a potential chemotherapeutic agent against breast cancer of the ERalpha-negative and ERbeta-positive type. Therefore, the objective of the present study was to determine whether the proliferative effects of genistein were caused by its activity as a selective ERbeta agonist or merely as an antiestrogen.


METHODS
This study was carried out in MDA-MB-231 (ERbeta) and T47D (ERalpha and ERbeta) human breast cancer cells. Cell proliferation was determined by the MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) assay. The cells were grown in estrogen-starved media and exposed to genistein at different concentrations for 72 h, either in the presence or absence of 17beta-estradiol.


RESULTS
A significant decrease in cell proliferation was seen in MDA-MB-231 cells at low concentrations of genistein in the presence of 17beta-estradiol, as compared to genistein alone. In T47D cells, which are known to have a predominance of ERalpha over ERbeta, genistein showed a biphasic cell proliferative response both in the presence and absence of 17beta-estradiol.


CONCLUSIONS
Our results suggest that in cells with a predominance of ERalpha, genistein acts as an agonist to ERalpha, and in cells with ERbeta alone, genistein most likely acts as an antiestrogen. Our results also suggest that genistein could be useful as a chemotherapeutic agent in premenopausal women with breast cancer of the ERalpha-negative and ERbeta-positive type.
Rajah
Talitha T
TT
Department of Biological Sciences, DePaul University, Chicago, IL, USA. trajah@depaul.edu
Du
Nga
N
Drews
Neil
N
Cohn
Rachel
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D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D048789:Phytoestrogens; D004958:Estradiol; D019833:Genistein