Inhibition of telomerase activity by oleanane triterpenoid CDDO-Me in pancreatic cancer cells is ROS-dependent.
Inhibition of telomerase activity by oleanane triterpenoid CDDO-Me in pancreatic cancer cells is ROS-dependent.
复制标题
DOI：
10.3390/molecules18033250
复制
发表时间：
2013-03-13
期刊：
影响因子：
--
通讯作者：
Gautam SC
中科院分区：
文献类型：
--
作者：
Deeb D;Gao X;Liu Y;Varma NR;Arbab AS;Gautam SC
甲基-2-氰基-3，12-二氧代齐墩果烷-1，9（11）-二烯-28-酸酯（CDDO-Me）是一种合成的三萜油酸衍生物，在广泛的癌细胞中具有促凋亡活性。CDDO-Me诱导细胞凋亡与活性氧（ROS）的产生和端粒酶活性的抑制有关。在本研究中，我们研究了ROS在CDDO-me抑制端粒酶中的作用。用CDDO-Me处理胰腺癌细胞系MiaPaCa-2和Panc-1，诱导过氧化氢和超氧阴离子的产生，并抑制端粒酶活性。用N-乙酰半胱氨酸（一种通用抗氧化剂）或谷胱甘肽过氧化物酶（GPx）或超氧化物歧化酶-1（SOD-1）的过表达预处理细胞阻断了CDDO-Me的端粒酶抑制活性。此外，阻断ROS的产生也阻止了CDDO-Me对hTERT基因表达、hTERT蛋白产生和许多hTERT调节蛋白表达的抑制（例如，c-Myc、Sp1、NF-κB和p-Akt）。数据还显示Akt在端粒酶活性的激活中起重要作用。总之，这些数据表明，抑制端粒酶活性的CDDO-Me是通过ROS依赖性机制介导的;然而，需要更多的工作来充分了解ROS在下调hTERT基因和hTERT调节蛋白的CDDO-Me的作用。
Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a synthetic derivative of oleanolic acid, a triterpene, with apoptosis-inducing activity in a wide range of cancer cells. Induction of apoptosis by CDDO-Me is associated with the generation of reactive oxygen species (ROS) and inhibition of telomerase activity. In the present study, we investigated the role of ROS in inhibition of telomerase by CDDO-me. Treatment of MiaPaCa-2 and Panc-1 pancreatic cancer cell lines with CDDO-Me induced the production of hydrogen peroxide and superoxide anions and inhibited the telomerase activity. Pretreatment of cells with N-acetylcycsteine, a general purpose antioxidant or overexpression of glutathione peroxidase (GPx) or superoxide dismutase-1 (SOD-1) blocked the telomerase inhibitory activity of CDDO-Me. Furthermore, blocking ROS generation also prevented the inhibition of hTERT gene expression, hTERT protein production and expression of a number of hTERT–regulatory proteins by CDDO-Me (e.g., c-Myc, Sp1, NF-κB and p-Akt). Data also showed that Akt plays an important role in the activation of telomerase activity. Together, these data suggest that inhibition of telomerase activity by CDDO-Me is mediated through a ROS-dependent mechanism; however, more work is needed to fully understand the role of ROS in down-regulation of hTERT gene and hTERT-regulatory proteins by CDDO-Me.
登录
查看更多内容
DOI：
10.3390/molecules171214795
发表时间：
2012-12-11
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Liu Y;Gao X;Deeb D;Arbab AS;Gautam SC
通讯作者：
Gautam SC
影响因子：
5.2
作者：
Deeb D;Gao X;Arbab AS;Barton K;Dulchavsky SA;Gautam SC
通讯作者：
Gautam SC
影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
影响因子：
11.2
作者：
Chintharlapalli, Sudhakar;Papineni, Sabitha;Safe, Stephen
通讯作者：
Safe, Stephen
影响因子：
7.4
作者：
Lee, Seung J.;Seo, Kyo W.;Kim, Chi D.
通讯作者：
Kim, Chi D.