title: Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC-7721 cells.
abstract: The activation of human telomerase, a process regulated by the human telomerase reverse transcriptase (hTERT), is a crucial step during cellular immortalization and malignant transformation. We have reported that gambogic acid (GA), a natural product isolated from the gamboge resin of Garcinia hanburyi tree, is an effective telomerase inhibitor and thus displays potent anticancer activity both in vitro and in vivo. Here we present the direct interaction of GA with oncogene c-MYC, a ubiquitous transcription factor involved in the control of cell proliferation and differentiation, as the molecular mechanism of GA's inhibitory effect on telomerase activity. Consistent with the recently reported association between c-MYC overexpression and induction of telomerase activity, we find here that GA treatment of a human hepatoma cell line SMMC-7721 significantly reduced the expression of c-MYC in a time- and concentration-dependent manner accompanied with the down-regulation of the hTERT transcription and the ultimate reduction in telomerase activity. Our results indicate that the hTERT is a target of c-MYC activity and identify a feasible mechanism of GA's potent anticancer activity.
authors.affiliation: Department of Physiology, China Pharmaceutical University, 24 Tongjiaxian, Nanjing 210009, China. qinglongguo@hotmail.com
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
authors.forename: Sen-Sen
authors.initials: SS
authors.lastname: Lin
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Qi
authors.forename: Fei
authors.initials: F
authors.lastname: Liang
authors.forename: Zi
authors.initials: Z
authors.lastname: Tan
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D044004:Xanthones; C052659:gambogic acid; D019098:Telomerase