9‐Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells

FEBS Letters

Sato, Norihiro¹  Maehara, Naoki¹  Kusumoto, Masahiro¹  Mizumoto, Kazuhiro¹  Ogawa, Takahiro¹  Tanaka, Masao¹  Niiyama, Hideaki¹ 

[1] Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka 812-8582, Japan

关键词: 9-Hydroxyellipticine;    Telomerase activity;    Inhibitor;    Protein kinase;   

DOI  :  10.1016/S0014-5793(98)01571-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

There is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular immortality and carcinogenesis. We hypothesized that 9-hydroxyellipticine (9-HE), an antitumor alkaloid, would inhibit telomerase activity because the drug has a unique mechanism of inhibiting phosphorylation of mutant p53 protein via inhibition of protein kinases, thereby restoring wild-type p53 function. This study was conducted to examine the effect of 9-HE on telomerase activity in human pancreatic cancer cells with differing p53 gene status. 9-HE treatment at relatively high concentrations resulted in rapid, complete inhibition of telomerase activity, irrespective of the p53 status. We conclude that 9-HE may exert a strong inhibitory effect on telomerase activity possibly through inhibition of protein kinases rather than through restoration of functional wild-type p53.

【 授权许可】

Unknown