Synergistic Effects of Inecalcitol With Imatinib and Dasatinib on Chronic Myeloid Leukemia Cell Lines.

Abstract

According to American Cancer Society's recent estimates, about 5,330 men and 3,950 women are diagnosed each year with chronic myeloid leukemia (CML). Roughly, 750 men and 530 women are predicted to die as a result of CML, establishing a dire need for advancements in CML treatment. Tyrosine kinase inhibitors (TKIs) imatinib and dasatinib have profound effects for prognosis and delaying survival from CML. The role of inecalcitol in the treatment and prevention of various cancers including leukemia has been established. The aim of this study was to analyze the putative synergistic treatment effects of inecalcitol in combination with imatinib or dasatinib on various cell lines including AR-230, LAMA-84-s, KCL-22, and U-937. Cells grown in plates were treated alone or with varying combinations of inecalcitol, imatinib, and dasatinib and incubated for 48 h at 37°C. Cell death was determined using MTT assay. KCL-22 and U-937 were resistant to both combination treatments, whereas AR-230 exhibited a maximal antiproliferative effect (24%) with the combined treatment of imatinib (0.325 μM) and inecalcitol (15.8 μM) (p<0.001). With dasatinib (0.456 nM) and inecalcitol (15.8 μM), AR-230 exhibited a 34% antiproliferative effect (p<0.001). In drastic contrast, LAMA84-s exhibited a 45% antiproliferative effect (with the combined treatment of imatinib (0.325 μM) and inecalcitol (15.8 μM) (p<0.006). Notably, with dasatinib (0.456 nM) and inecalcitol (15.8 μM), LAMA84-s exhibited approximately 78% cell killing (p<0.007). The study suggests that the synergistic effects of inecalcitol with imatinib on cell killing are more drastic in some cells than others. These varying effects may be due to differences in cell metabolism.