Rajah Talitha T, Du Nga, Drews Neil, Cohn Rachel
Department of Biological Sciences, DePaul University, Chicago, IL, USA.
Pharmacology. 2009;84(2):68-73. doi: 10.1159/000226123. Epub 2009 Jun 26.
BACKGROUND/AIM: 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. METHOD: 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.
背景/目的：染料木黄酮是大豆中的一种成分，已显示在乳腺癌细胞中具有双相增殖作用，高浓度（>10微摩尔/升）时抑制体外细胞增殖，而低浓度（<10微摩尔/升）时刺激细胞增殖。然而，流行病学研究表明染料木黄酮的摄入量与乳腺癌发病率呈负相关。这种差异的一个可能原因可能是雌激素受体（ERα和/或ERβ）的不同状态。染料木黄酮以高亲和力选择性地与ERβ结合，因此可能是一种针对ERα阴性和ERβ阳性型乳腺癌的潜在化疗药物。因此，本研究的目的是确定染料木黄酮的增殖作用是由其作为选择性ERβ激动剂的活性引起的，还是仅仅作为一种抗雌激素引起的。 方法：本研究在MDA-MB-231（ERβ）和T47D（ERα和ERβ）人乳腺癌细胞中进行。通过MTT（3-[4,5-二甲基-2-噻唑基]-2,5-二苯基-2H-四唑溴盐）试验测定细胞增殖。细胞在雌激素缺乏的培养基中生长，并在有或没有17β-雌二醇的情况下，以不同浓度暴露于染料木黄酮72小时。 结果：与单独使用染料木黄酮相比，在存在17β-雌二醇的情况下，低浓度染料木黄酮使MDA-MB-231细胞的细胞增殖显著降低。在已知ERα比ERβ占优势的T47D细胞中，无论有无17β-雌二醇，染料木黄酮均显示出双相细胞增殖反应。 结论：我们的结果表明，在以ERα为主的细胞中，染料木黄酮作为ERα的激动剂起作用，而在仅含ERβ的细胞中，染料木黄酮很可能作为抗雌激素起作用。我们的结果还表明，染料木黄酮可能作为一种化疗药物用于绝经前ERα阴性和ERβ阳性型乳腺癌妇女。
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