Repression of telomerase reverse transcriptase mRNA and hTERT promoter by gambogic acid in human gastric carcinoma cells.

Abstract:

OBJECTIVES:To investigate the effects and potential mechanisms of gambogic acid (GA), a naturally occurring anticancer agent, on the expression and regulation of telomerase in human gastric carcinoma cells. METHODS:GA-induced inhibition of cell proliferation was evaluated by the commonly employed MTT assay on two human gastric carcinoma cell lines, MGC-803 and SGC-7901. Telomerase activity and hTERT mRNA expression were determined by telomeric repeat amplication protocol-polymerase chain reaction and reverse transcription-polymerase chain reaction, respectively. The hTERT promoter activity was measured by luciferase assay. The expression of c-MYC, an apoptotic gene that modulates the expression of hTERT promoter, was quantified by Western blotting. RESULTS:The proliferation of human gastric carcinoma cell lines, MGC-803 and SGC-7901, was significantly inhibited with GA treatment. Both telomerase activity and hTERT mRNA expression were notably decreased in cells treated with GA. The activity of hTERT promoter and the expression of c-MYC were also remarkably decreased in GA-treated cells. CONCLUSION:This study demonstrated that GA treatment of human gastric carcinoma cell lines, MGC-803 and SGC-7901, 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

Yu J,Guo QL,You QD,Lin SS,Li Z,Gu HY,Zhang HW,Tan Z,Wang X

doi

10.1007/s00280-005-0177-2

keywords:

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

434-43

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

58

pub_type

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