Department of Surgery, Henry Ford Health System, Detroit, MI 48202, USA.
Biochem Biophys Res Commun. 2012 Jun 15;422(4):561-7. doi: 10.1016/j.bbrc.2012.05.024. Epub 2012 May 16.
Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a multifunctional oleanane synthetic triterpenoid with potent anti-inflammatory and antitumorigenic properties. The mechanisms of the antisurvival and apoptosis-inducing activities of CDDO-Me and related derivatives of oleanolic acid have been defined; however, to date, no study has been carried out on the effect of CDDOs on human telomerase reverse transcriptase (hTERT) gene or telomerase activity. Here we report for the first time that inhibition of cell proliferation and induction of apoptosis by CDDO-Me in pancreatic cancer cell lines is associated with the inhibition of hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT expression and activity. Furthermore, abrogation or overexpression of hTERT protein altered the susceptibility of tumor cells to CDDO-Me. These findings suggest that telomerase (hTERT) is a relevant target of CDDO-Me in pancreatic cancer cells.
2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-酸甲酯（CDDO-Me）是一种具有强大抗炎和抗肿瘤特性的多功能齐墩果烷合成三萜。CDDO-Me 和相关的齐墩果酸衍生物的抗生存和诱导凋亡活性的机制已经确定；然而，迄今为止，尚未有关于 CDDO 对人端粒酶逆转录酶（hTERT）基因或端粒酶活性的影响的研究。在这里，我们首次报道 CDDO-Me 在胰腺癌细胞系中抑制细胞增殖和诱导细胞凋亡与抑制 hTERT 基因表达、hTERT 端粒酶活性以及调节 hTERT 表达和活性的多种蛋白质有关。此外，hTERT 蛋白的缺失或过表达改变了肿瘤细胞对 CDDO-Me 的敏感性。这些发现表明，端粒酶（hTERT）是 CDDO-Me 在胰腺癌细胞中的一个相关靶点。
