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: N Sato, K Mizumoto, M Kusumoto, H Niiyama, N Maehara, T Ogawa, M Tanaka
• Journal: FEBS letters (FEBS Lett) Vol. 441 Issue 2 Pg. 318-21 (Dec 18 1998) ISSN: 0014-5793 [Print] England
• PMID: 9883907 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• DNA Primers
• Ellipticines
• Enzyme Inhibitors
• 9-hydroxyellipticine
• Telomerase

Topics

• Antimetabolites, Antineoplastic (pharmacology)
• Base Sequence
• DNA Primers
• Ellipticines (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Genes, p53
• Humans
• Pancreatic Neoplasms (enzymology, genetics, pathology)
• Substrate Specificity
• Telomerase (antagonists & inhibitors, metabolism)
• Tumor Cells, Cultured