Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3
Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3
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DOI：
10.1093/carcin/bgm148
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发表时间：
2007-11-01
期刊：
影响因子：
4.7
通讯作者：
Banerjee, Partha P.
中科院分区：
文献类型：
--
作者：
Chau, My N.;El Touny, Lara H.;Banerjee, Partha P.
端粒酶通过调节生长因子和凋亡蛋白而赋予癌细胞增殖和存活，从而有助于癌细胞的无限复制潜力。虽然它是众所周知的植物雌激素，染料木黄酮，具有端粒酶抑制和抗增殖作用的各种癌细胞在药理学浓度，我们在这里报告，生理上可实现浓度的染料木黄酮增强端粒酶活性，人前列腺癌细胞的增殖和肿瘤生长的转基因小鼠前列腺腺癌模型。在确定增强端粒酶活性的机制中，我们观察到生理浓度的金雀异黄素在体外和体内激活信号转导和转录激活因子3（STAT3），并增加STAT3与人前列腺癌细胞中端粒酶逆转录酶启动子的结合。这些结果第一次证明，生理上可达到的浓度的染料木黄酮通过激活STAT3增强前列腺癌细胞中的端粒酶逆转录酶转录活性。因此，染料木黄酮的这些浓度将增加前列腺癌细胞的生长，这可能对患有前列腺癌的个体有害，因此，当考虑染料木黄酮用于化疗目的时应谨慎。
Telomerase contributes to the infinite replicative potential of cancer cells by conferring proliferation and survival through the regulation of growth factors and apoptotic proteins. Although it is generally known that the phytoestrogen, genistein, has telomerase-repressing and anti-proliferative effects on various cancer cells at pharmacological concentrations, we report here that physiologically achievable concentrations of genistein enhance telomerase activity, the proliferation of human prostate cancer cells and tumor growth in the transgenic adenocarcinoma mouse prostate model. In determining the mechanism for enhanced telomerase activity, we observed that physiological concentrations of genistein activated signal transducers and activators of transcription 3 (STAT3) both in vitro and in vivo and increased STAT3 binding to the telomerase reverse transcriptase promoter in human prostate cancer cells. These results demonstrate for the first time that physiologically achievable concentrations of genistein enhance telomerase reverse transcriptase transcriptional activity in prostate cancer cells via the activation of STAT3. Consequently, these concentrations of genistein will augment the growth of prostate cancer cells that could be detrimental to individuals with prostate cancer and therefore, caution should be exercised when genistein is considered for chemotherapeutic purposes.