Authors
Abstract
Introduction: Telomere maintenance is essential for the continued proliferation of dividing cells, and is implicated in chromosome stability and cell immortalization. Telomerase activity, that allows cancer cells to maintain their telomeric DNA for an indefinite replicative capacity, is an attractive target against cancer. A well known benzylisoquinoline alkaloid, papaverine, we focused on to evaluate its antiproliferaive effects on breast cancer MCF7 cells.
Methods: Cytotoxicity of the commercially available pure compound papaverine HCl (Sigma) was determined by MTT assay. A modified quantitative real-time polymerase chain reaction (PCR)-based telomerase repeat amplification protocol (TRAP) was used to estimate relative telomerase activity in papaverine-treated cells in comparison with the untreated control cells. Relative expression level of the catalytic subunit of telomerase (hTERT) gene was estimated using real time reverse transcription-PCR (RT-PCR).
Results: IC50 concentration of papaverine after 48 hours treatment was measured to 120 micromolar. At this concentration telomerase activity showed a considerable decrease (almost 70% in comparison with untreated control cells), in a concentration dependent manner. Quantitative real-time RT-PCR experiments indicated a similar reduction in transcription level of hTERT gene under treatment with papaverine.
Conclusion: Papaverine is a potent natural compound in suppression of cancer cell immortality most probably by anti-telomerase activity. It is a valuable putative compound for further development of promising anti-cancer agents.
Keywords
)