Background and Purpose:Trans-resveratrol (RSVL; 3,4′,5-trihydroxystilbene), a natural compound found in grapes, berries, peanuts and red wine exerts certain anticancer roles in different human cancer types. However, the exact molecular mechanism(s) behind such a role remains to be elucidated, thus the aim of this study. Experimental Approach: T47D human breast cancer cells were treated with RSVL and cell proliferation was measured by cell counting. Apoptosis was analyzed by Giemsa staining, poly(ADP-ribose) polymerase (PARP) fragmentation analysis and annexin V assay. Regulation of p53 tumor suppressor protein, p70S6K, and pS6 ribosomal protein was measured by detecting their phosphorylated active forms using ECL-immunoblot analysis. Results: The present results show that RSVL-induced growth inhibition in T47D cells is caused by apoptosis as demonstrated by morphological changes and PARP fragmentation. RSVL-induced apoptosis is associated with the activation of the p53 in a dose- and a time-dependent manner. Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002 abolished the effect of RSVL on p53 activation. Interestingly, RSVL inhibits the expression of p70S6K and the phosphorylation of pS6RP. Conclusions and Implications: These findings demonstrate that RSVL affects multiple intracellular signaling transduction pathways such as p53 activation/protein translation inhibition/apoptosis, and strongly support a contemplated use of this natural compound as a preventive and/or an adjuvant therapeutic drug for breast cancer. The data indicate that these proteins may be used as predictive biomarkers to evaluate the treatment efficacy of RSVL in clinical trials.

This content is only available via PDF.
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.