Cytotoxic effect of 6-Shogaol in Imatinib sensitive and resistant K562 cells.

Abstract

Chronic Myeloid Leukemia (CML) is a clonal hematopoietic malignancy characterized by the formation of BCR-ABL fusion protein. Imatinib (IMA) is a BCR-ABL tyrosine kinase inhibitor (TKI), which exhibited a high rate of response for newly diagnosed CML patients. Emergence of IMA resistance considered as a major challenge in CML therapy. Recent studies reported the anti-cancer effect of natural extracts such as 6-Shogaol (6-SG) which is extracted from ginger and the mechanisms involved in targeting of cancer cells. In the present study, we aimed to explore the potential anticancer effect of 6-SG on K562S (Imatinib sensitive) and K562R (Imatinib resistant) cells. K562S and K562R cells were incubated with increasing concentrations of 6-SG (5μM- 50μM) to determine its cytotoxic and apoptotic effects. Cell viability and apoptosis were investigated with spectrophotometric MTT assay and flow cytometric Annexin V staining, respectively. The mRNA expression levels of apoptotic related genes (BAX and BCL-2) and drug transporter (MDR-1 and MRP-1) genes were evaluated with qRT-PCR. According to our results, 6-SG treatment inhibited cell viability, induced apoptosis in both K562S and K562R cells. Based on our RT-PCR results, 6-SG enhanced pro-apoptotic BAX gene and decreased anti-apoptotic BCL-2 gene expression levels significantly in both treated K562S and K562R cells. Furthermore, 6-SG increased MDR-1 mRNA expression level in K562S and K562R cells in comparison with their control counterparts. Whereas, 6-SG decrease MRP-1 mRNA expression level in K562S cells significantly. It is the first study that reveals the apoptotic effect of 6-SG in CML cell line and IMA resistance. Therefore, 6-SG treatment can be suggested as a promising strategy for CML therapy.