Telomerase Reverse Transcriptase (TERT) is a Therapeutic Target of Oleanane Triterpenoid CDDO-Me in Prostate Cancer

Molecules

Yongbo Liu¹  Xiaohua Gao¹  Dorrah Deeb¹  Ali S. Arbab¹ 

[1] ¹Department of General Surgery, Henry Ford Health System, Detroit, MI 48202, USA ²Department of Radiology, Henry Ford Health System, Detroit, MI 48202, USA

关键词: CDDO-Me;    hTERT;    telomerase activity;    apoptosis;    prostate cancer;   

DOI  :  10.3390/molecules171214795

来源: mdpi

【 摘 要 】

Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is an synthetic oleanane triterpenoid with strong antiprolifertive and proapoptotic activities in cancer cells. However, the effect of CDDO-Me on human telomerase reverse transcriptase (hTERT) and its telomerase activity in prostate cancer cells has not been studied. We investigated the role of hTERT in mediating the anticancer activity of CDDO-Me in prostate cancer cells in vitro and in vivo. The inhibition of cell proliferation and induction of apoptosis by CDDO-Me in LNCaP and PC-3 prostate cancer cell lines was associated with the inhibition of hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT transcriptionally and post-translationally. Furthermore, ablation of hTERT protein increased the sensitivity of cancer cells to CDDO-Me, whereas its overexpression rendered them resistant to CDDO-Me. In addition, inhibition of progression of preneoplastic lesions (i.e., low and high-grade prostate intraepithelial neoplasms, PINs) to adenocarcinoma of the prostate by CDDO-Me in TRAMP mice was associated with significant decrease in TERT and its regulatory proteins in the prostate gland. These data provide evidence that telomerase is a potential target of CDDO-Me for the prevention and treatment of prostate cancer.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.