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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 21, 2006 Accepted August 8, 2006 Resveratrol inhibits proliferation, induces apoptosis and overcomes chemoresistance through downregulation of STAT3 and nuclear factor-B-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells Anjana Bhardwaj, Gautam Sethi, Saroj Vadhan-Raj, Carlos Bueso-Ramos, Yasunari Takada, Upasna Gaur, Asha S. Nair, Shishir Shishodia, and Bharat B. Aggarwal* Dept. of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX Dept. of Cytokine & Supportive Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX Dept. of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX * Corresponding author; email: aggarwal{at}mdanderson.org. 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 Velcade 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 downregulation 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 downregulated 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 examined CD 138+ plasma cells from MM patients, resveratrol inhibited constitutive activation of both NF-B and STAT3 leading to downregulation of cell proliferation and potentiation of apoptosis induced by Velcade 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: B. Sung, A. B. Kunnumakkara, G. Sethi, P. Anand, S. Guha, and B. B. Aggarwal Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model Mol. Cancer Ther., April 1, 2009; 8(4): 959 - 970. [Abstract] [Full Text] [PDF] M. K. Pandey, B. Sung, K. S. Ahn, and B. B. Aggarwal Butein Suppresses Constitutive and Inducible Signal Transducer and Activator of Transcription (STAT) 3 Activation and STAT3-Regulated Gene Products through the Induction of a Protein Tyrosine Phosphatase SHP-1 Mol. Pharmacol., March 1, 2009; 75(3): 525 - 533. [Abstract] [Full Text] [PDF] B. B. Aggarwal, R.V. Vijayalekshmi, and B. Sung Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe Clin. Cancer Res., January 15, 2009; 15(2): 425 - 430. [Abstract] [Full Text] [PDF] 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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