Evaluation of the effect of genistein and oleuropein on the expression of genes involved in drug resistance in acute myeloid leukemia cell lines HL-60 and KG1

Abstract

Leukemias are characterized as malignancies of white blood cells, which are linked to the excessive growth of hematopoietic cells and bone marrow failure. Among these, acute myeloid leukemia (AML) predominantly affects older individuals and has a mortality rate of approximately 80%. While chemotherapy drugs used to treat AML can also impact normal cells, drug resistance and disease recurrence pose significant challenges to its treatment. Consequently, the utilization of natural compounds such as oleuropein and genistein offers a potential solution by enhancing the effectiveness of chemotherapy drugs while minimizing side effects. This study aimed to examine the impact of oleuropein and genistein on the expression levels of BAX, BCL2, MDR1 and MRP1 genes in acute myeloid leukemia cell lines HL-60 and KG1. Material and methods: In this investigation, the MTT assay was employed to determine the IC50 dosage of genistein, oleuropein and the combined drug treatment in two different cell lines. Subsequently, the cells were subjected to drug administration. Following 24, 48, and 72 hours of cell treatment, the Real Time PCR technique was utilized to assess the expression levels of BAX, MDR1, MRP, and BCL2 genes. Results: Following the application of cell treatment and conducting the MTT test, it was observed that both oleuropein and genistein exhibit cytotoxic properties. Furthermore, the synergistic effect of combining these two compounds enhances their cytotoxicity. The Real Time PCR analysis corroborates these findings by demonstrating that the combination of these drugs leads to a reduction in the expression of BCL2, MDR1, and MRP genes, while simultaneously increasing the expression of BAX gene.