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Chris Brigolin
Chris Brigolin
Tanzania
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Research Article
Induction of Apoptosis in Pancreatic Cancer Cells by CDDO-Me Involves Repression of Telomerase through Epigenetic Pathways
Author(s): Dorrah Deeb, Chris Brigolin, Xiaohua Gao, Yongbo Liu, Kirit R. Pindolia and Subhash C. GautamDorrah Deeb, Chris Brigolin, Xiaohua Gao, Yongbo Liu, Kirit R. Pindolia and Subhash C. Gautam
Reactivation of telomerase in cancers provides an attractive target for developing novel agents to selectively destroy tumor cells. Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me), a synthetic oleanane triterpenoid, inhibited and induced apoptosis in pancreatic cancer cells at very low concentrations. The antiproliferative and apoptosis-inducing effects of CDDO-Me were associated with the inhibition of human telomerase reverse transcriptase (hTERT) mRNA, hTERT protein and reduction in hTERT telomerase activity. CDDO-Me inhibited multiple transcription factors that regulate hTERT expression positively (Sp1, c-Myc and NF-κB) and negatively (CTCF, E2F-1 and MAD1). CDDO-Me inhibited protein levels of DNA methyl transferases DNMT1 and DNMT3a, which also resulted in hypomethylation of hTERT promoter. In addition, transcriptionally active chromatin markers, such as acety.. View More»
DOI: 10.4172/2157-2518.1000177