Original Paper

Caffeic Acid Phenethyl Ester Induces Apoptosis of Human Pancreatic Cancer Cells Involving Caspase and Mitochondrial Dysfunction
Ming-Jen Chen^a, Wen-Hsiung Chang^a, Ching-Chung Lin^a, Chia-Yuan Liu^a, Tsang-En Wang^a, Cheng-Hsin Chu^a, Shou-Chuan Shih^a, Yu-Jen Chen<sup>b

a</sup>Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital and Mackay Medicine, Nursing and Management College, Taipei, and
^bDepartment of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan (ROC)

Address of Corresponding Author

Pancreatology 2008;8:566-576 (DOI: 10.1159/000159843)

  Key Words

• Pancreatic cancer
• Caffeic acid phenethyl ester
• Apoptosis
• BxPC-3 cells
• Caspase
• Mitochondrial dysfunction

  Abstract

Aims: 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 µg/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-G₁ cells was partially blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk (50 µM) 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.

Copyright © 2008 S. Karger AG, Basel and IAP

  Author Contacts

Yu-Jen Chen
Department of Radiation Oncology, Mackay Memorial Hospital
No. 92, Sec. 2, Chungshan North Road, Taipei, Taiwan (ROC)
Tel. +886 2 2809 4661, ext. 3060, Fax +886 2 2809 6180
E-Mail chenmdphd@yahoo.com

  Article Information

Received: May 29, 2007
Accepted after revision: November 27, 2007
Published online: September 29, 2008
Number of Print Pages : 11
Number of Figures : 7, Number of Tables : 0, Number of References : 40