Huang Pei-Rong, Yeh Yuan-Ming, Wang Tzu-Chien V
Department of Molecular and Cellular Biology, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan, ROC.
Cancer Lett. 2005 Sep 28;227(2):169-74. doi: 10.1016/j.canlet.2004.11.045. Epub 2004 Dec 24.
Telomerase activity is repressed in normal human somatic cells, but is activated in most cancers, suggesting that telomerase may be an important target for cancer therapy. Inhibition of telomerase in cancer cells has been shown to limit the growth of human cancer cells in culture. In this study, we report that helenalin, a natural sesquiterpene lactone, is a potent and selective inhibitor for human telomerase. In vitro studies indicate that this drug can inactivate telomerase directly in a manner that is dependent on concentration and time. The inhibitory action of this drug on telomerase is selective since the presence of excessive externally added proteins did not protect the inhibition and all of the other enzymes tested in this study were not inhibited by this drug. Furthermore, we demonstrated that helenalin can inhibit the expression of hTERT and telomerase in hematopoietic cancer cells. Therefore, the anti-tumor activity of helenalin is attributed, at least in part, to the inhibition of telomerase.
端粒酶活性在正常人体体细胞中受到抑制，但在大多数癌症中被激活，这表明端粒酶可能是癌症治疗的一个重要靶点。已证明抑制癌细胞中的端粒酶可限制培养的人类癌细胞的生长。在本研究中，我们报告了海伦内酯，一种天然倍半萜内酯，是一种有效的、选择性的人类端粒酶抑制剂。体外研究表明，这种药物可以以浓度和时间依赖性的方式直接使端粒酶失活。这种药物对端粒酶的抑制作用具有选择性，因为过量添加外部蛋白质并不能保护其抑制作用，并且在本研究中测试的所有其他酶都不受该药物抑制。此外，我们证明海伦内酯可以抑制造血癌细胞中hTERT和端粒酶的表达。因此，海伦内酯的抗肿瘤活性至少部分归因于对端粒酶的抑制。
