Background: Sanguinarine is a benzophenanthridine alkaloid that is known to have antimicrobial, anti-inflammatory, antioxidant and anticancer properties. In this study, we examined the effects of this compound on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death using a human breast carcinoma MDA-MB-231 cell line. Methods: Cytotoxicity was evaluated by trypan blue exclusion methods. Apoptosis was detected using DAPI staining, agarose gel electrophoresis and flow cytometer. The expression levels of proteins were determined by Western blot analyses and caspase activities were measured using colorimetric assays. The ROS production and mitochondrial membrane potential (MMP, ΔΨm) changes were measured fluorimetrically. Results: The results of this study demonstrate that sanguinarine mediates ROS production, and that this mediation is followed by a decrease in MMP, the release of cytochrome c, activation of caspase-9 and caspase-3, and downregulation of antiapoptosis factor XIAP and cIAP-1. Sanguinarine also promoted the activation of caspase-8 and truncation of Bid (tBid). Moreover, the quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the sanguinarine-induced apoptosis effects via inhibition of ROS production, MMP collapse, tBid expression and the subsequent activation of caspases. These observations clearly indicate that ROS are involved in the early molecular events in the sanguinarine-induced apoptotic pathway. Conclusion: Our data imply that sanguinarine-induced ROS are key mediators of MMP collapse, which leads to the release of cytochrome c followed by caspase activation, culminating in apoptosis.

Keywords:
Sanguinarine, Apoptosis, Reactive oxygen species, Mitochondrial membrane potential
This content is only available via PDF.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
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.
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 government 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.
You do not currently have access to this content.