title: Role of telomerase in anticancer activity of pristimerin in prostate cancer cells.
abstract: Pristimerin (PM) is a quinonemethide triterpenoid present in various plant species with strong antiprolifertive and proapoptotic activities in cancer cells. The effect of PM on telomerase which is reactivated in most cancers including carcinoma of the prostate (CaP) has not been studied. We investigated the effect of PM on the expression of human telomerase reverse transcriptase (hTERT) gene that codes for the catalytic subunit of the telomerase holoenzyme complex in prostate cancer cell lines LNCaP and PC-3 cells. The inhibition of cell proliferation and induction of apoptosis by PM in both cell lines was associated with the inhibition of hTERT mRNA expression, suppression of native and phosphorylated hTERT protein and hTERT telomerase activity. The ablation of hTERT expression increased the sensitivity of cancer cells to PM. In addition, results also revealed that the inhibition of hTERT expression is attributed to the inhibition of transcription factors SP1, c-Myc and STAT3 and protein kinase B/Akt which regulate hTERT transcriptionally and post-translationally, respectively. These data provide evidence that telomerase is a potential target of PM in prostate cancer.
authors.forename: Yong Bo
authors.initials: YB
authors.lastname: Liu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gao
authors.forename: Dorrah
authors.initials: D
authors.lastname: Deeb
authors.forename: Kirit
authors.initials: K
authors.lastname: Pindolia
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Gautam
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D053978:Pentacyclic Triterpenes; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger; D014315:Triterpenes; C509186:TERT protein, human; D019098:Telomerase; C050414:celastrol