Double-edge Effect of Caffeic Acid Phenethyl Ester (CAPE) on Intracellular Reactive Oxygen Species and Apoptosis in NB4 Leukemia Cells
Date Issued
2009
Date
2009
Author(s)
Cheng, I-Cheng
Abstract
Caffeic acid phenethyl ester (CAPE), an active component from bee propolis, has been recognized as a strong antioxidant agent. However, several previous documents report the pro-oxidant effect of CAPE. In this investigation to specify the role of CAPE on intracellular intracellular reactive oxygen species (ROS), we report CAPE acts either as a protective antioxidant at early phase of treatment or a deleterious pro-oxidant during late time period to human promyelocytic NB4 cells. This double-edged effect of CAPE depended on the treatment time phase rather than the dose. Short-term CAPE treatment was protective due to the induction of heme-oxygenase-1 (HO-1) at an appropriate level which catalyzed anti-oxidative heme degradation. Long-term CAPE treatment was deleterious because overexpression of HO-1 led to inhibition of ferritin and thereby the transient existence of ferrous iron, which in turn reacted with hydrogen peroxide through the Fenton reaction to produce more-harmful hydroxyl radicals. The pro-oxidative nature also is involved in CAPE-induced typical mitochondrion-dependent apoptosis. The molecular mechanism of CAPE-driven apoptosis is associated with multiple Bcl-2 family proteins including inhibition of Bcl-2 and Mcl-1 and up-regulation of Bmf, Noxa, and Bax. The results of interaction of those Bcl-2 family proteins cause loss of mitochondrial membrane potential and leaking of Cytochrome c, and subsequently activate Caspase-9 and Caspase -3 to complete the intrinsic apoptotic signal finally. The conclusion of this dissertation suggests that CAPE (or propolis containing CAPE) could be a potential candidate for cancer therapy in the clinic and should be applied carefully.
Subjects
propolis
caffeic acid phenethyl ester
reactive oxygen species
apoptosis
leukemia
SDGs
Type
thesis
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