Yj. Chen et al., The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells, ANTI-CANC D, 12(2), 2001, pp. 143-149
Caffeic acid phenethyl ester (CAPE), an active component of propolis, has m
any biological and pharmacological activities including antioxidation and t
umor cell cytotoxicity. We examined the type of cell death in human leukemi
c HL-60 cells after CAFE treatment in order to elucidate the relationship b
etween CAFE-induced alterations of the redox state and apoptosis. CAFE trea
tment (6 mug/ml) resulted in marked growth inhibition up to 70.3 +/- 4.0% a
t day 2. This inhibition was partially blocked by pretreatment with N-acety
l-L-cycteine (NAC), Agarose gel electrophoresis showed evident DNA fragment
ation after CAFE treatment. CAFE induced a significant decrease in mitochon
drial 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 depl
etion and partially rescued cells from CAPE-induced apoptosis. With regard
to intracellular reactive oxygen species, CAFE caused a fast and profound s
cavenging 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 scav
enging of H2O2 in human leukemic HL-60 cells. [(C) 2001 Lippincott Williams
& Wilkins.].