Anti-proliferative effects of chelerythrine by telomerase inhibition in MCF-7 cell line

Introduction: Telomere maintenance is essential for the continued proliferationof dividing cells, and is implicated in chromosome stability and cellimmortalization. Immortality of cancer cells is mainly due to the activation ofthe reverse transcriptase ribonucleoprotein telomerase. Telomerase activity thatallows cancer cells to maintain their telomeric DNA for an indefinite replicativecapacity, is an attractive target against cancer.Material and Methods: Here we studied the probable effects of chelerythrineHCl on telomerase activity in MCF-7 cancer cells. In order to investigate themolecular effect of this compound on telomerase activity, first we estimated theIC50 concentration in cultured cells. Cytotoxicity of the commercially availablepure compound chelerythrine HCl (Sigma) was determined by MTT assay. Amodified quantitative real-time polymerase chain reaction -based telomeraserepeat amplification protocol (q-TRAP) was used to estimate relativetelomerase activity in chelerythrine-treated cells in comparison with theuntreated control cells.Results: IC50 of chelerythrine after 48 h treatment was measured as 2.6 μM,while at this concentration relative telomerase activity in equal amount ofprotein from each sample showed strong inhibition to almost 52% of untreatedcontrol cells.Conclusion: The results presented here indicate that chelerythrine is a highlypotent anti-telomerase among natural compounds with a good potential forfurther development as a promising anti-cancer agent.

Keywords:

Telomerase , Cancer , chelerythrine