shogaol and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

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 (5 μM- 50 μM) 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.

Topics: Apoptosis; ATP Binding Cassette Transporter, Subfamily B; bcl-2-Associated X Protein; Catechols; Cell Proliferation; Drug Resistance, Neoplasm; Fusion Proteins, bcr-abl; Gene Expression Regulation, Neoplastic; Humans; Imatinib Mesylate; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multidrug Resistance-Associated Proteins; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-bcl-2