標題: | Butylidenephthalide Suppresses Human Telomerase Reverse Transcriptase (TERT) in Human Glioblastomas |
作者: | Lin, Po-Cheng Lin, Shinn-Zong Chen, Yi-Lin Chang, Jeng-Shou Ho, Li-Ing Liu, Po-Yen Chang, Li-Fu Harn, Yeu-Chern Chen, Shee-Ping Sun, Li-Yi Huang, Pi-Chun Chein, Jung-Ting Tsai, Chang-Hai Chou, Chii-Wen Harn, Horng-Jyh Chiou, Tzyy-Wen 生物科技學系 Department of Biological Science and Technology |
公開日期: | 1-十一月-2011 |
摘要: | Telomerase is widely expressed in most human cancers, but is almost undetectable in normal somatic cells and is therefore a potential drug target. Using the human telomerase promoter platform, the naturally occurring compound butylidenephthalide (BP) was selected for subsequent investigation of antitumor activity in vitro and in vivo. We treated human glioblastoma cells with BP and found a dose-dependent decrease in human telomerase reverse transcriptase (hTERT) mRNA expression and a concomitant increase in p16 and p21 expression. Because c-Myc and Sp1 are involved in transcriptional regulation of hTERT, the effect of BP on c-Myc and Sp1 expression was examined. Using electrophoretic mobility shift assays and western blotting, we showed that BP represses hTERT transcriptional activity via downregulation of Sp1 expression. Using the telomerase repeat amplification protocol, an association between BP concentration and suppression of telomerase activity, induction of human glioblastoma senescence, and inhibition of cellular proliferation was identified. This was supported by a mouse xenograft model, in which BP repressed telomerase and inhibited tumor proliferation, resulting in tumor senescence. Overexpression of hTERT restored telomerase activity in human glioblastoma cells and overcame replicative senescence. These findings suggest that BP inhibits proliferation and induces senescence in human glioblastomas by downregulating hTERT expression and consequently telomerase activity. This is the first study to describe regulation of telomerase activity by BP in human glioblastomas. |
URI: | http://dx.doi.org/10.1245/s10434-011-1644-0 http://hdl.handle.net/11536/14711 |
ISSN: | 1068-9265 |
DOI: | 10.1245/s10434-011-1644-0 |
期刊: | ANNALS OF SURGICAL ONCOLOGY |
Volume: | 18 |
Issue: | 12 |
起始頁: | 3514 |
結束頁: | 3527 |
顯示於類別: | 期刊論文 |