Differential sensitivity to resveratrol-induced apoptosis of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells

The in vitro effects of resveratrol (RES) on apoptotic pathway in human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells were investigated. RES treatment of both cell types significantly and irreversibly inhibited their growth, associated with extensive apoptosis and increase in hypodiploid cells. Cell cycle analysis showed accumulation in G1 phase in HSB-2 drug exposed cells, while only K562-treated cells exhibited a marked accumulation in S phase with a concomitant decrease in G1 and G2/M at 24h. Moreover, RES caused internucleosomal DNA fragmentation, even if K562 cells were found less sensitive to the drug, as compared to HSB-2 cells, which also reacted earlier to the treatment. RES-induced apoptosis was associated with an increase of Bax expression and a marked release of cytochrome c from mitochondria. Interestingly, K562 cells exhibited a basal content of glutathione 10-fold that of HSB-2 cells, which increased after 24–48h RES exposure, together with increment of glutathione reductase and peroxidase activities. However, the major resistance to apoptosis of K562 cells cannot be attributed to their higher pool of reducing power, since neither the inhibition of glutathione synthesis by buthionine sulphoximine nor glutathione depletion by diethylmaleate, sensitized these cells. In addition, glutathione enrichment of HSB-2 cells by N-acetylcysteine did not prevent the apoptotic effects of RES. Our data indicate that RES commitment to apoptosis in both cell lines is independent from the intracellular content of glutathione, while it is associated with either the enhanced expression of Bax and cytochrome c release. [Copyright &y& Elsevier]