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首页> 外文期刊>Life sciences >Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC-7721 cells.
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Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC-7721 cells.

机译：藤黄酸抑制人端粒酶逆转录酶基因在人肝癌SMMC-7721细胞中的表达。

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摘要

The activation of human telomerase, a process regulated by the human telomerase reverse transcriptase (hTERT), is a crucial step during cellular immortalization and malignant transformation. We have reported that gambogic acid (GA), a natural product isolated from the gamboge resin of Garcinia hanburyi tree, is an effective telomerase inhibitor and thus displays potent anticancer activity both in vitro and in vivo. Here we present the direct interaction of GA with oncogene c-MYC, a ubiquitous transcription factor involved in the control of cell proliferation and differentiation, as the molecular mechanism of GA's inhibitory effect on telomerase activity. Consistent with the recently reported association between c-MYC overexpression and induction of telomerase activity, we find here that GA treatment of a human hepatoma cell line SMMC-7721 significantly reduced the expression of c-MYC in a time- and concentration-dependent manner accompanied with the down-regulation of the hTERT transcription and the ultimate reduction in telomerase activity. Our results indicate that the hTERT is a target of c-MYC activity and identify a feasible mechanism of GA's potent anticancer activity.
机译：人端粒酶的激活是人类端粒酶逆转录酶（hTERT）调控的过程，是细胞永生化和恶性转化过程中的关键步骤。我们已经报道，藤黄酸（GA）是一种从汉藤树藤黄树脂中分离出来的天然产物，是一种有效的端粒酶抑制剂，因此在体外和体内均显示出有效的抗癌活性。在这里，我们介绍了GA与癌基因c-MYC的直接相互作用，后者是一种参与细胞增殖和分化控制的普遍存在的转录因子，是GA抑制端粒酶活性的分子机制。与最近报道的c-MYC过表达和端粒酶活性的诱导之间的关联一致，我们在这里发现，GA治疗人肝癌细胞系SMMC-7721会以时间和浓度依赖性方式显着降低c-MYC的表达并伴随hTERT转录的下调和端粒酶活性的最终降低。我们的结果表明，hTERT是c-MYC活性的靶标，并确定了GA有效的抗癌活性的可行机制。

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