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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2293-2302. Prepublished online as a Blood First Edition Paper on December 12, 2006; DOI 10.1182/blood-2006-02-003988. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-003988v1 109/6/2293    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bhardwaj, A. Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Bhardwaj, A. Articles by Aggarwal, B. B. Related Collections Apoptosis Signal Transduction Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-B–regulated antiapoptotic and cell survival gene products in human multiple myeloma cells Anjana Bhardwaj1, Gautam Sethi1, Saroj Vadhan-Raj,2, Carlos Bueso-Ramos3, Yasunari Takada1, Upasna Gaur1, Asha S. Nair1, Shishir Shishodia1, and Bharat B. Aggarwal1 1 Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston; 2 Department of Cytokine and Supportive Oncology, The University of Texas M.D. Anderson Cancer Center, Houston; 3 Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston Whether resveratrol, a component of red grapes, berries, and peanuts, could suppress the proliferation of multiple myeloma (MM) cells by interfering with NF-B and STAT3 pathways, was investigated. Resveratrol inhibited the proliferation of human multiple myeloma cell lines regardless of whether they were sensitive or resistant to the conventional chemotherapy agents. This stilbene also potentiated the apoptotic effects of bortezomib and thalidomide. Resveratrol induced apoptosis as indicated by accumulation of sub-G1 population, increase in Bax release, and activation of caspase-3. This correlated with down-regulation of various proliferative and antiapoptotic gene products, including cyclin D1, cIAP-2, XIAP, survivin, Bcl-2, Bcl-xL, Bfl-1/A1, and TRAF2. In addition, resveratrol down-regulated the constitutive activation of AKT. These effects of resveratrol are mediated through suppression of constitutively active NF-B through inhibition of IB kinase and the phosphorylation of IB and of p65. Resveratrol inhibited both the constitutive and the interleukin 6–induced activation of STAT3. When we examined CD138+ plasma cells from patients with MM, resveratrol inhibited constitutive activation of both NF-B and STAT3, leading to down-regulation of cell proliferation and potentiation of apoptosis induced by bortezomib and thalidomide. These mechanistic findings suggest that resveratrol may have a potential in the treatment of multiple myeloma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Puissant, S. Grosso, A. Jacquel, N. Belhacene, P. Colosetti, J.-P. Cassuto, and P. Auberger Imatinib mesylate-resistant human chronic myelogenous leukemia cell lines exhibit high sensitivity to the phytoalexin resveratrol FASEB J, June 1, 2008; 22(6): 1894 - 1904. [Abstract] [Full Text] [PDF] A. M. Roccaro, X. Leleu, A. Sacco, A.-S. Moreau, E. Hatjiharissi, X. Jia, L. Xu, B. Ciccarelli, C. J. Patterson, H. T. Ngo, et al. Resveratrol Exerts Antiproliferative Activity and Induces Apoptosis in Waldenstrom's Macroglobulinemia Clin. Cancer Res., March 15, 2008; 14(6): 1849 - 1858. [Abstract] [Full Text] [PDF] S. A. Gatz and L. Wiesmuller Take a break--resveratrol in action on DNA Carcinogenesis, February 1, 2008; 29(2): 321 - 332. [Abstract] [Full Text] [PDF] A. Sors, F. Jean-Louis, E. Begue, L. Parmentier, L. Dubertret, M. Dreano, G. Courtois, H. Bachelez, and L. Michel Inhibition of I{kappa}B Kinase Subunit 2 in Cutaneous T-Cell Lymphoma Down-Regulates Nuclear Factor-{kappa}B Constitutive Activation, Induces Cell Death, and Potentiates the Apoptotic Response to Antineoplastic Chemotherapeutic Agents Clin. Cancer Res., February 1, 2008; 14(3): 901 - 911. [Abstract] [Full Text] [PDF]

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