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

Anticancer Drugs. 2001 Feb;12(2):143-9. doi: 10.1097/00001813-200102000-00008.


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 CAPE treatment in order to elucidate the relationship between CAPE-induced alterations of the redox state and apoptosis. CAPE treatment (6 microg/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 CAPE treatment. CAPE induced a significant decrease in mitochondrial transmembrane potential to about half 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, CAPE caused a fast and profound scavenging of H202 (19% of untreated cells after a 2-h treatment) but not of superoxide anion. These results suggest that apoptosis induced by CAPE is associated with mitochondrial dysfunction, GSH depletion and selective scavenging of H2O2 in human leukemic HL-60 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Caffeic Acids / pharmacology*
  • Catalase / metabolism
  • Cell Cycle / drug effects
  • Cytotoxins / pharmacology*
  • DNA Damage / drug effects
  • DNA, Neoplasm / analysis
  • Glutathione / metabolism
  • HL-60 Cells / drug effects*
  • HL-60 Cells / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Oxidation-Reduction
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology*
  • Reactive Oxygen Species
  • Superoxides / metabolism


  • Antioxidants
  • Caffeic Acids
  • Cytotoxins
  • DNA, Neoplasm
  • Reactive Oxygen Species
  • Superoxides
  • Hydrogen Peroxide
  • Catalase
  • caffeic acid phenethyl ester
  • Glutathione
  • Phenylethyl Alcohol
  • Acetylcysteine