Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL-60 cells

Pycnogenol, rich of many phytochemicals of medical value, is it commercialized nutrient supplement extracted from the bark of European coastal pine. In this study, we investigated the anti-tumor effects of Pycnogenol on HL-60, U937 and K562 human leukemia cell lines. We found that Pycnogenol inhibited cell proliferation dose- and time-dependently and the IC(50)s of Pycnogenol on HL-60, U937 and K562 cells were 150, 40 and 100 mu g/ml, respectively. When HL-60 cells were incubated with low concentrations of Pycnogenol (50, 100 and 125 mu g/ml) for 24 h. a prominent GO/G1 arrest was observed. followed by gradual accumulation of sub-G0/G1 nuclei. At 48 h of treatment, 50-70% of HL-60 cells differentiated, as evidenced by morphological changes, NBT reduction, induction of NSE activity, and increases of cell surface expression of CD11b. However. results front Annexin V/PI staining, DAPI staining and DNA fragmentation assay indicated that Pycnogenol induced HL-60. U937 and K562 cell apoptosis at their respective IC(50)s after 24 h of treatments. Pretreatment of z-DEVD-fmk, a caspase-3 specific inhibitor. not only decreased caspase-3 activity but also reduced the percentage of: apoptotic cells induced by Pycnogenol. This indicated that caspase-3 activation was involved in Pycnogenol induced-apoptosis. In conclusion, Pycnogenol induced differentiation and apoptosis in leukemia cells. Our data suggest that Pycnogenol could serve Lis a potent cancer chemopreventive or chemotherapeutic agent for human leukemia. (c) 2004 Elsevier Ltd. All rights reserved.