title: Triptolide inhibits transcription of hTERT through down-regulation of transcription factor specificity protein 1 in primary effusion lymphoma cells.
abstract: Primary effusion lymphoma (PEL) is a rare and aggressive non-Hodgkin's lymphoma. Human telomerase reverse transcriptase (hTERT), a key component responsible for the regulation of telomerase activity, plays important roles in cellular immortalization and cancer development. Triptolide purified from Tripterygium extracts displays a broad-spectrum bioactivity profile, including immunosuppressive, anti-inflammatory, and anti-tumor. In this study, it is investigated whether triptolide reduces hTERT expression and suppresses its activity in PEL cells. The mRNA and protein levels of hTERT were examined by real time-PCR and Western blotting, respectively. The activity of hTERT promoter was determined by Dual luciferase reporter assay. Our results demonstrated that triptolide decreased expression of hTERT at both mRNA and protein levels. Further gene sequence analysis indicated that the activity of hTERT promoter was suppressed by triptolide. Triptolide also reduced the half-time of hTERT. Additionally, triptolide inhibited the expression of transcription factor specificity protein 1(Sp1) in PEL cells. Furthermore, knock-down of Sp1 by using specific shRNAs resulted in down-regulation of hTERT transcription and protein expression levels. Inhibition of Sp1 by specific shRNAs enhanced triptolide-induced cell growth inhibition and apoptosis. Collectively, our results demonstrate that the inhibitory effect of triptolide on hTERT transcription is possibly mediated by inhibition of transcription factor Sp1 in PEL cells.
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Long
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China; State Key Laboratory of Virology, Wuhan University, Wuhan, 430072, PR China. Electronic address: xsun6@whu.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Sun
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage*; D015536:Down-Regulation / Q000187:drug effects; D004852:Epoxy Compounds / Q000008:administration & dosage; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000378:metabolism* / Q000473:pathology; D010616:Phenanthrenes / Q000008:administration & dosage*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D019098:Telomerase / Q000037:antagonists & inhibitors*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C001899:triptolide; D019098:Telomerase
keywords: PEL cells; Sp1; Triptolide; hTERT