THE EFFECT OF TELOMERASE INHIBITOR MST-312 ON APOPTOSIS OF ACUTE LYMPHOBLASTIC LEUKEMIA CELL LINE NALM-6

Background and Objectives: There have been continuous efforts in telomerase-targeted therapy for cancer treatment because telomerase expression is significantly increased in about 85- 90% of human cancers while its expression is usually silenced in normal cells.
Materials and Methods: Throughout this experimental study, NALM-6 cells were treated with different concentrations of telomerase inhibitor, MST-312 at different times. Then, cell viability and metabolic activity were evaluated by trypan blue and MTT assays; cell apoptosis was also evaluated by flow cytometry using Annexin V Apoptosis Detection Kit. In addition, the expression of BAX and BCL2 genes was evaluated in the treated cells using Quantitative Real-time PCR.
Results: A dose-and time-dependent decrease was observed in the viability of NALM-6 cells after exposure with different concentration of MST-312. Over 50% decrease was observed in the viability of the cells treated with 8 mM of MST-312 after 48 h. The cytotoxic effect of MST-312 was dose- dependent, with approximately 6, 19.69 and 56.9% reduction in metabolic activity of NALM-6 cells after 48 h exposure with 2, 4, and 8 mM of MST-312, respectively. Approximately 20% apoptosis was observed in NALM-6 cells treated with 4mM of MST-312 after 48 h. Gene expression analysis also showed that 4mM of MST-312 led to upregulation of BAX and downregulation of Bcl-2 genes Conclusions Inhibition of telomerase activity by MST-312 can be proposed as a new candidate for the treatment of acute lymphoblastic leukemia.