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-Nov-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
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