Gambogic Acid Inhibits Proliferation of Human Lung Carcinoma SPC-A1 Cells in Vivo and in Vitro and Represses Telomerase Activity and Telomerase Reverse Transcriptase mRNA Expression in the Cells

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Abstract
We determined the in vivo and in vitro antitumor activities of gambogic acid (GA) and one of the possible mechanisms for its inhibitory activities. In vivo antitumor activity of GA was evaluated by the relative tumor growth ratio (T/C) in nude mice, and in vitro inhibition of SPC-A1 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and trypan blue exclusion assay. Telomere repeats amplification protocol (TRAP)-polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used to quantitatively detect telomerase activity and the expression of human telomerase reverse transcriptase (hTERT) mRNA, respectively. Results from our in vivo study showed that transplantable tumor growth remained suppressed for up to 21 d with minimal animal weight loss in nude mice treated with gambogic acid (i.v.). Proliferation of SPC-A1 cells cultured in vitro was significantly inhibited (p<0.01), showing time-dependent and dose-dependent inhibition. Telomerase activity and hTERT mRNA expression were both decreased significantly, when cells were exposed to gambogic acid for 24, 48 and 72 h (for 24 h p<0.05, and for 48, 72 h, p<0.01). These results suggeste that gambogic acid could inhibit the growth of SPC-A1 cells and its tumor xenografts, and when treated with gambogic acid for a period of time, telomerase activity and expression of hTERT mRNA in the tumor cells were both inhibited significantly. It is safe, at least in part, to conclude that the down-regulating telomerase activity of GA by modifying partly the expression of hTERT mRNA in SPC-A1 cells may be one possible mechanism for the inhibitory activity of GA in the cells.