Comparison of the effect of two drugs STA-21 and RESVERATOL; Inhibitors of STAT3 signaling proteins on AML-HL60 cells

Abstract

AML or acute myeloid leukemia is a type of myeloid blood cell leukemia that accelerates the growth and accumulation of white cells in the bone marrow and disrupts the production of normal blood cells. AML occurs at any age. But it is more common in people over 60 years old. In the treatment of AML, chemotherapy and natural products play an important role [1]. The usual treatments of this disease are usually associated with systemic toxicity and the risk of recurrence of the disease. Therefore, therapeutic efforts are focused on finding strategies that can target and destroy cancer cells without affecting healthy cells. New treatments for AML have been identified in signal transduction pathways, such as the STAT3 pathway. Recent studies have shown that the use of drugs that inhibit the JAK-STAT3 pathway, such as STA-21 and resveratrol, can reduce the cytotoxic effect induced on HL-60 cells.

Materials and methods: In this descriptive study, IC50 dose for two drugs STA-21 and RESVERATROL was determined in HL-60 cell line using MTT test. Then the cells were treated with two mentioned drugs. After 24, 48 and 72 hours of cell treatment, the amount of apoptosis induced in them was measured using flow cytometry technique. Also, the expression and methylation of the promoter of the candidate genes were investigated before and after the treatment using RT-PCR and MS-QPCR (methylation specific-quantitative PCR).

Result: The results showed that the simultaneous use of two drugs, Resveratrol and STA-21, by inhibiting the JAK-STAT3 pathway, decreased the expression of BCL-2 and increased the methylation of BCL-2, increased the expression of BAX and caspase 6, and decreased the methylation of BAX and Caspase6 and also have a cytotoxic effect on HL-60 cells. This result was in line with the results of apoptosis investigation by flow cytometry technique.