Majallah-i Dānishgāh-i ̒Ulūm-i Pizishkī-i Bābul (Mar 2021)
Cytotoxic and Apoptotic Effects of C-Myc Inhibition by 10058-F4 on Acute Promyelocytic Leukemia Cells
Abstract
BACKGROUND AND OBJECTIVE: C-Myc plays a very important role in controlling cell proliferation, apoptosis and differentiation. Due to the involvement of c-Myc in the regulation of a wide range of intracellular functions and based on its role in the pathogenesis of acute promyelocytic leukemia (APL), the present study was conducted to investigate the anti-leukemia effect of 10058-F4, as a known c-Myc inhibitor, on APL-derived HL-60 cells. METHODS: In this experimental study, to evaluate the cytotoxic effects of 10058-F4 in acute promyelocytic leukemia, HL-60 cell line (prepared from Pasteur Institute of Iran) was treated with different doses of inhibitor (50, 100, 150 and 200 μM) and then in 24 -and 36- hours intervals, survival rate, cell count, metabolic activity and induction of apoptosis were respectively evaluated. In addition, transcriptional changes of apoptosis-related genes were studied by real-time PCR to investigate the molecular mechanisms of function of 10058-F4. FINDINGS: The results showed that inhibition of c-Myc by 10058-F4 at doses of 150 and 200 μM in 24 hours reduced the growth of HL-60 cells by 38±4% and 49±3.2%, respectively, compared to the control group (p<0.05). In addition, the cytotoxic effects of the drug are due to the arrest of cells in the G1 phase and the induction of apoptosis; Because the percentage of cells stained with Annexin V/PI in cells treated at a dose of 100 μM after 24 hours increased by 31% compared to the control group (p<0.05). CONCLUSION: In this study, the efficacy of 10058-F4 in HL-60 cells was fully established.
