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

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  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

  Publication Details

Pancreatology

Vol. 8, No. 6, Year 2008 (Cover Date: October 2008)

Journal Editor: Urrutia R. (Rochester, Minn.)
ISSN: 1424-3903 (Print), eISSN: 1424-3911 (Online)

For additional information: http://www.karger.com/PAN

  Drug Dosage / Copyright

Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.