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Molecules 2013, 18(3), 3250-3265; doi:10.3390/molecules18033250

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

Department of General Surgery, Henry Ford Health System, Detroit, MI 48202, USA
Department of Radiology Research, Henry Ford Health System, Detroit, MI 48202, USA
Author to whom correspondence should be addressed.
Received: 31 January 2013 / Revised: 27 February 2013 / Accepted: 6 March 2013 / Published: 13 March 2013
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
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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.
Keywords: pancreatic cancer; CDDO-Me; ROS; hTERT; telomerase activity pancreatic cancer; CDDO-Me; ROS; hTERT; telomerase activity
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Deeb, D.; Gao, X.; Liu, Y.; Varma, N.R.S.; Arbab, A.S.; Gautam, S.C. Inhibition of Telomerase Activity by Oleanane Triterpenoid CDDO-Me in Pancreatic Cancer Cells is ROS-Dependent. Molecules 2013, 18, 3250-3265.

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