NDLI: Inhibition of Telomerase Activity by Oleanane Triterpenoid CDDO-Me in Pancreatic Cancer Cells is ROS-Dependent

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Inhibition of Telomerase Activity by Oleanane Triterpenoid CDDO-Me in Pancreatic Cancer Cells is ROS-Dependent

Content Provider	PubMed Central
Author	Deeb, Dorrah Gao, Xiaohua Liu, Yongbo Varma, Nadimpalli R. S. Arbab, Ali S. Gautam, Subhash C.
Copyright Year	2013
Abstract	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.
Related Links	http://dx.doi.org/10.3390/molecules18033250
Ending Page	3265
Page Count	16
Starting Page	3250
File Format	PDF
ISSN	14203049
e-ISSN	14203049
Journal	Molecules (Basel, Switzerland)
Issue Number	3
Volume Number	18
Language	English
Publisher Date	2013-03-01
Access Restriction	Open
Subject Keyword	Organic Chemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Medicine Drug Discovery Analytical Chemistry Physical and Theoretical Chemistry Molecular Medicine Pharmaceutical Science

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