ISSN : 2146-3123
E-ISSN : 2146-3131

Cytotoxic Effects of Some Flavonoids and Imatinib on K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method
Ferdane Danışman Kalındemirtaş1, Hüsniye Birman1, Eda Candöken2, Sema Bilgiş Gazioğlu3, Gülay Melikoğlu4, Serap Kuruca1
1Department of Physiology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
2Department of Biochemistry, İstanbul University İstanbul School of Pharmacy, İstanbul, Turkey
3Department of Immunology, Istanbul University Institute of Experimental Medicine, İstanbul, Turkey
4Department of Pharmacognosy, İstanbul University İstanbul School of Pharmacy, İstanbul, Turkey
DOI : 10.4274/balkanmedj.2017.1244

Background: Flavonoids, known as natural compounds have antioxidant, anticarcinogenic, and anti-inflammatory effects.
Aim: This study aim to determine the cytotoxic effects of flavonoids and drug resistance related P-gp on K562 human chronic myeloid leukemia cells. We also aim to evaluate of theurapeutic potential for imatinib and flavonoid combinations.
Study Design: Cell culture study.
Materials and Methods: In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and imatinib mesylate, an anticancer drug. The effect of flavonoids on K562 cell proliferation was detected using MTT assay. Concentrations of apigenin, luteolin, 5-desmethyl sinensetin ranging from 25 to 200 µM and imatinib 5 to 50 µM for 72 h were studied. Apoptosis/necrosis and P-gp activity was measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated with combination index value using CompuSyn software.
Results: In our study, IC50 values for apigenin, luteolin, and 5-desmethyl sinensetin were found as 140 μM, 100 μM, and >200 μM respectively. Luteolin (100 μM) was found the most effective when we compared the cytotoxic activity of these flavonoids. These results are statistically significant (p < 0.05). Luteolin and imatinib combinations were the most effective and recommendable for cytotoxic activity in K562 cell line among the flavonoids that we studied. After 72 hours of incubation at IC50 concentrations, all flavonoids had about 50% apoptotic effect on the cells. P-gp activity was increased in all groups. Combination treatment may provide better outcomes and reduce the use of imatinib dosages for cytotoxicity.
Conclusion: Although imatinib and some tyrosine kinase inhibitors is widely used in the treatment of chronic myeloid leukemia, more effective new drug research continues. An advantage of using drug combinations is that this would let cells to be given lower doses of anticancer drugs because of each drug can act through different mechanisms. Finally, the combination of these flavonoids and imatinib mesylate was able to enhance the cytotoxic effect but the antagonistic effect should be considered in the combined use for K562 cells.

Keywords : K562, apigenin, luteolin, sinensetin, P-gp, apoptosis, combination index
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