Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

BACKGROUND: Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects. AIMS: To determine the cytotoxic effects of flavonoids and drug resistance related to P-gp on K562 human chronic myeloid leukemia cells. We also aimed to evaluate the therapeutic potential of imatinib and flavonoid combinations. STUDY DESIGN: Cell culture study. METHODS: In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and the anticancer drug imatinib mesylate. The effect of flavonoids on K562 cell proliferation was detected using the 3-(4,5-dimethylthiazolyl)2,5‑diphenyl‑tetrazolium bromide assay. Concentrations of apigenin, luteolin, and 5-desmethyl sinensetin ranging from 25 to 200 μM and of imatinib from 5 to 50 μM administered for 72 h were studied. Apoptosis/necrosis and P-gp activity were measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated according to combination index values calculated using CompuSyn software. RESULTS: In our study, the IC(50) values for apigenin, luteolin, and 5-desmethyl sinensetin were found to be 140 μM, 100 μM, and >200 μM, respectively. Luteolin (100 μM) had the highest cytotoxic activity of these flavonoids. These results were statistically significant (p<0.05). Among the flavonoids studied, the combination of luteolin and imatinib was the most effective and is therefore recommended for its cytotoxic activity in the K562 cell line. After 72 h of incubation at their respective IC(50) concentrations, all flavonoids were associated with an apoptosis rate of approximately 50%. P-glycoprotein activity was increased in all groups. Combination treatment may provide better outcomes in terms of cytotoxicity and thus reduce the dosages of imatinib used. CONCLUSION: The combination of some flavonoids and imatinib mesylate may increase the cytotoxic effect; However, the antagonistic effect should be considered in combined use on k562 cells.