9-hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells

There is increasing interest in identifying potent inhibitors of telomerase because the enzyme plays a crucial role in the development of cellular imm ortality and carcinogenesis, We hypothesized that 9-hydroxyellipticine (9-H E), an antitumor alkaloid, mould inhibit telomerase activity because the dr ug has a unique mechanism of inhibiting phosphorylation of mutant p53 prote in via inhibition of protein kinases, thereby restoring wild-type p53 funct ion. This study mas conducted to examine the effect of 9-HE on telomerase a ctivity 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 concl ude that 9-HE may exert a strong inhibitory effect on telomerase activity p ossibly through inhibition of protein kinases rather than through restorati on of functional wild-type p53. (C) 1998 Federation of European Biochemical Societies.