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

Leuk Res. 2005 Jun;29(6):685-92. doi: 10.1016/j.leukres.2004.10.006. Epub 2005 Jan 19.


Pycnogenol, rich of many phytochemicals of medical value, is a 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 microg/ml, respectively. When HL-60 cells were incubated with low concentrations of Pycnogenol (50, 100 and 125 microg/ml) for 24 h, a prominent G0/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 from 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 as a potent cancer chemopreventive or chemotherapeutic agent for human leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / drug effects
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • DNA / drug effects
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology*
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / pathology
  • Plant Extracts
  • Time Factors
  • U937 Cells


  • Flavonoids
  • Plant Extracts
  • pycnogenols
  • DNA
  • CASP3 protein, human
  • Caspase 3
  • Caspases