THE WINE POLYPHENOL RESVERATROL MODULATES AUTOPHAGY AND INDUCES APOPTOSIS IN MOLT-4 AND HL-60 HUMAN LEUKEMIA CELLS

Resveratrol is a naturally occurring polyphenolic compound present in many plant species and wine. It possesses a wide range of beneficial biological properties including anticancer activity. Resveratrol has been demonstrated to induce both autophagy and apoptosis in several human cancer cell lines. The aim of this study was to investigate whether resveratrol modulates autophagy and apoptosis in MOLT-4 human lymphoblastic leukemia and HL-60 human promyelocytic leukemia cells. Cell viability was evaluated by the neutral red uptake assay. Cell cycle distribution, phosphatidylserine externalization, caspase-3 activation, changes of the mitochondrial membrane potential, intracellular production of reactive oxygen species were evaluated by flow cytometry. LC3-I to LC3-II conversion was examined based on Western blotting and immunofluorescence analyses. The level of p62/SQSTM1 protein and PARP1 cleavage were analyzed by Western blotting. The DNA degradation was assessed by gel electrophoresis. We found that resveratrol is able to modulate autophagy in MOLT-4 and HL-60 cells, as evidenced by the detection of an increased level of LC3-II and p62/SQSTM1 proteins. Moreover, resveratrol induced apoptosis in both cell lines which was associated with phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. The present study provides evidence that resveratrol can act as an autophagy modulator as well as an apoptosis inducer in MOLT-4 and HL-60 human leukemia cells. Our findings imply that resveratrol can be a promising chemotherapeutic agent in the treatment of leukemia.