Antiproliferative Effect of the Isoquinoline Alkaloid Papaverine in Hepatocarcinoma HepG-2 Cells — Inhibition of Telomerase and Induction of Senescence

Molecules

Sakineh Kazemi Noureini¹ 

[1] Department of Biology, Faculty of Science, Hakim Sabzevari University, P.O. Box 397, Sabzevar, Iran

关键词: papaverine;    telomerase;    immortality;    senescence;   

DOI  :  10.3390/molecules190811846

来源: mdpi

【 摘 要 】

Cancer cells are often immortal through up-regulation of the hTERT gene, which encodes the catalytic subunit of a special reverse transcriptase to overcome end-replication problem of chromosomes. This study demonstrates that papaverine, an isoquinoline alkaloid from the Papaveraceae, can overcome telomerase dependent immortality of HepG-2 cells that was used as a model of hepatocarcinoma. Although this alkaloid does not directly interact with telomeric sequences, papaverine inhibits telomerase through down-regulation of hTERT, which was analysed using thermal FRET and qRT-PCR, respectively. The IC₅₀ values for the reduction of both telomerase activity and hTERT expression was 60 µM, while IC₅₀ for cytotoxicity was 120 µM. Repeated treatments of the cells with very low non-toxic concentrations of papaverine resulted in growth arrest and strong reduction of population doublings after 40 days. This treatment induced senescent morphology in HepG-2 cells, which was evaluated by beta-galactosidase staining. Altogether, papaverine can be regarded as a promising model compound for drug design targeting cancer development.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.