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 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.
Sato
N
N
Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Mizumoto
K
K
Kusumoto
M
M
Niiyama
H
H
Maehara
N
N
Ogawa
T
T
Tanaka
M
M
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
D000964:Antimetabolites, Antineoplastic; D017931:DNA Primers; D004611:Ellipticines; D004791:Enzyme Inhibitors; C008009:9-hydroxyellipticine; D019098:Telomerase