Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction.
OBJECTIVE
This study aimed to investigate the effect of caffeic acid phenethyl ester (CAPE), an active component isolated from honeybee propolis, in inducing apoptosis in human pancreatic cancer cells.


METHODS
Inhibition of viability of BxPC-3 and PANC-1 cell lines induced by CAPE was estimated by a trypan blue dye exclusion test. The type of cell death in BxPC-3 after CAPE treatment was characterized by observation of morphology, sub-G1 DNA content, annexin-V/PI staining, caspase-3 and caspase-7 assay, and DNA agarose gel electrophoresis.


RESULTS
CAPE (10 microg/ml) resulted in marked inhibition of viability of BxPC-3 (80.4 +/- 4.1%) and PANC-1 (74.3 +/- 2.9%) cells. CAPE induced a time-dependent increase in hypodiploid percentage and a significant decrease in mitochondrial transmembrane potential in BxPC-3 cells. It induced morphological changes of typical apoptosis, but no DNA fragmentation was noted by DNA electrophoresis. The inhibition of growth and increased in the proportion of sub-G(1) cells was partially blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk (50 microM) in BxPC-3 cells indicating a caspase-related mechanism in CAPE-induced apoptosis. Caspase-3/caspase-7 activity was approximately 2 times greater in CAPE-treated BxPC-3 cells compared with control cells.


CONCLUSIONS
These results suggest that CAPE is a potent apoptosis-inducing agent. Its action is accompanied by mitochondrial dysfunction and activation of caspase-3/caspase-7.
Chen
Ming-Jen
MJ
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan, ROC.
Chang
Wen-Hsiung
WH
Lin
Ching-Chung
CC
Liu
Chia-Yuan
CY
Wang
Tsang-En
TE
Chu
Cheng-Hsin
CH
Shih
Shou-Chuan
SC
Chen
Yu-Jen
YJ
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013379:Substrate Specificity; D013997:Time Factors
D000975:Antioxidants; D002109:Caffeic Acids; D020169:Caspases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol