title: 9-Hydroxyellipticine inhibits telomerase activity in human pancreatic cancer cells.
abstract: 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.
authors.affiliation: Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Mizumoto
authors.forename: M
authors.initials: M
authors.lastname: Kusumoto
authors.forename: H
authors.initials: H
authors.lastname: Niiyama
authors.forename: N
authors.initials: N
authors.lastname: Maehara
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D004611:Ellipticines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016158:Genes, p53; D006801:Humans; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013379:Substrate Specificity; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D017931:DNA Primers; D004611:Ellipticines; D004791:Enzyme Inhibitors; C008009:9-hydroxyellipticine; D019098:Telomerase