The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many biological and pharmacological activities including antioxidation and tumor cell cytotoxicity. We examined the type of cell death in human leukemic HL-60 cells after CAFE treatment in order to elucidate the relationship between CAFE-induced alterations of the redox state and apoptosis. CAFE treatment (6 mug/ml) resulted in marked growth inhibition up to 70.3 +/- 4.0% at day 2. This inhibition was partially blocked by pretreatment with N-acetyl-L-cycteine (NAC), Agarose gel electrophoresis showed evident DNA fragmentation after CAFE treatment. CAFE induced a significant decrease in mitochondrial transmembrane potential to about halt of the untreated level after 6 h and a rapid depletion of intracellular glutathione (GSH) down to 41.7 +/- 6.0% after 1 h. Pretreatment of HL-60 cells with NAC reversed the GSH depletion and partially rescued cells from CAPE-induced apoptosis. With regard to intracellular reactive oxygen species, CAFE caused a fast and profound scavenging of H2O2 (19% of untreated cells after a 2-h treatment) but not of superoxide anion. These results suggest that apoptosis induced by CAFE is associated with mitochondrial dysfunction, GSH depletion and selective scavenging of H2O2 in human leukemic HL-60 cells. [(C) 2001 Lippincott Williams & Wilkins.].