TY  - JOUR
TI  - Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method
AB  - 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 IC50 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 IC50 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.
AU  - GAZİOĞLU, Sema Bilgiç
AU  - BİRMAN, Hüsniye
AU  - ÇANDÖKEN, Eda
AU  - DANIŞMAN KALINDEMİRTAŞ, Ferdane
AU  - erdem kuruca, serap
AU  - Melikoğlu, Gülay
DO  - 10.4274/balkanmedj.galenos.2018.2017.1244
PY  - 2019
JO  - Balkan Medical Journal
VL  - 36
IS  - 2
SN  - 2146-3123
SP  - 96
EP  - 105
DB  - TRDizin
UR  - http://search/yayin/detay/318782
ER  -