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Table of Contents
Vol. 54, No. 3, 2008
Issue release date: July 2008
Section title: Pharmacology
Chemotherapy 2008;54:157–165
(DOI:10.1159/000140359)

Sanguinarine-Induced Apoptosis in Human Leukemia U937 Cells via Bcl-2 Downregulation and Caspase-3 Activation

Han M.H. · Yoo Y.H. · Choi Y.H.
aDepartment of Biomaterial Control (BK21 Program), Dongeui University Graduate School; bDepartment of Biochemistry, Dongeui University College of Oriental Medicine, and cDepartment of Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, Busan, South Korea

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Article / Publication Details

First-Page Preview
Abstract of Pharmacology

Received: 3/30/2007
Accepted: 11/26/2007
Published online: 6/18/2008

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

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

Abstract

Background: Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis, which induces apoptosis in human cancer cells, but the underlying action mechanisms are not completely understood. We investigated the mechanisms of sanguinarine on the induction of apoptosis using U937 leukemia cells. Methods: Cytotoxicity was evaluated by MTT assay. Apoptosis was detected using DAPI staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Casapse-3 activity was measured using a colorimetric assay. Results: Exposure of U937 cells to sanguinarine resulted in growth inhibition and induction of apoptosis. Apoptosis by sanguinarine treatment was associated with the activation of caspase-3 and degradation of poly-(ADP-ribose) polymerase (PARP) and phospholipase C-γ1 protein. Induction of apoptosis by sanguinarine was also accompanied by upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2 expression. Sanguinarine-induced caspase-3 activation and apoptosis were significantly attenuated in Bcl-2-overexpressing U937/Bcl-2 cells. Furthermore, a caspase-3-specific inhibitor blocked caspase-3 activation as well as PARP degradation, and increased the survival rate of sanguinarine-treated U937 cells. Conclusions: These results demonstrated that the induction of apoptosis by sanguinarine in U937 cells was associated with altering the balance of Bcl-2 and Bax protein expression and activation of the caspase-3 pathway.


Article / Publication Details

First-Page Preview
Abstract of Pharmacology

Received: 3/30/2007
Accepted: 11/26/2007
Published online: 6/18/2008

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

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


Copyright / Drug Dosage

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.
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.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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