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

Molecules

Dorrah Deeb¹  Xiaohua Gao¹  Yongbo Liu¹  Nadimpalli R. S. Varma²  Ali S. Arbab² 

[1] Department of General Surgery, Henry Ford Health System, Detroit, MI 48202, USA; E-Mails:;Department of Radiology Research, Henry Ford Health System, Detroit, MI 48202, USA; E-Mails:

关键词: pancreatic cancer;    CDDO-Me;    ROS;    hTERT;    telomerase activity;   

DOI  :  10.3390/molecules18033250

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.