Apoptotic Effects of Resveratrol, a Grape Polyphenol, on Imatinib-Sensitive and Resistant K562 Chronic Myeloid Leukemia Cells

Abstract

Aim: To examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. Materials and Methods: Antiproliferative effects of resveratrol were determined by the 3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) cell proliferation assay. Apoptotic effects of resveratrol on sensitive K562 and resistant K562/IMA-3 cells were determined through changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and apoptosis by annexin V-(FITC). Results: The concentrations of resveratrol that inhibited cell growth by 50% (IC50) were calculated as 85 and 122 mu M for K562 and K562/IMA-3 cells, respectively. There were 1.91-, 7.42- and 14.73-fold increases in loss of MMP in K562 cells treated with 10, 50, and 100 mu M resveratrol, respectively. The same concentrations of resveratrol resulted in 2.21-, 3.30- and 7.65-fold increases in loss of MMP in K562/IMA3 cells. Caspase-3 activity increased 1.04-, 2.77- and 4.8-fold in K562 and 1.02-, 1.41- and 3.46-fold in K562/IMA3 cells in response to the same concentrations of resveratrol, respectively. Apoptosis was induced in 58.7%- and 43.3% of K562 and K562/IMA-3 cells, respectively, in response to 100 mu M resveratrol. Conclusion: Taken together these results may suggest potential use of resveratrol in CML, as well as in patients with primary and/or acquired resistance to imatinib.