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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-11-3550. This Article Full Text (PDF) All Versions of this Article: 2002-11-3550v1 102/3/987    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 Estrov, Z. Articles by Aggarwal, B. B Search for Related Content PubMed PubMed Citation Articles by Estrov, Z. Articles by Aggarwal, B. B Social Bookmarking                   What's this? Submitted November 27, 2002 Accepted March 18, 2003 Resveratrol blocks interleukin-1-induced activation of the nuclear transcription factor NF-B, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells Zeev Estrov*, Shishir Shishodia, Stefan Faderl, David Harris, Quin Van, Hagop M Kantarjian, Moshe Talpaz, and Bharat B Aggarwal Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA * Corresponding author; email: zestrov{at}mdanderson.org. Resveratrol, an edible polyphenolic stilbene, has been reported to possess substantial antileukemic activities in different leukemia cell lines. We investigated whether resveratrol is active against fresh acute myeloid leukemia (AML) cells and its mechanism of action. Because interleukin (IL)-1 plays a key role in AML cell proliferation, we first tested the effect of resveratrol on the AML cell lines OCIM2 and OCI/AML3, both of which produce IL-1 and proliferate in response to it. Resveratrol inhibited proliferation of both cell lines in a dose-dependent fashion (5 to 75 µM) by arresting the cells at S phase, thus preventing their progression through the cell cycle; IL-1 partially reversed this inhibitory effect. Resveratrol significantly reduced production of IL-1 in OCIM2 cells. It also suppressed the IL-1-induced activation of transcription factor NF-B which modulates an array of signals controlling cellular survival, proliferation, and cytokine production. Indeed, incubation of OCIM2 cells with resveratrol resulted in apoptotic cell death. Because caspase inhibitors Ac-DEVD-CHO or z-DEVD-FMK partially reversed the antiproliferative effect of resveratrol we tested its effect on the caspase pathway and found that resveratrol induced the activation of the cysteine protease caspase 3 and subsequent cleavage of the DNA repair enzyme poly (ADP-ribose) polymerase. Finally, resveratrol suppressed colony-forming cell proliferation of fresh AML marrow cells from 5 patients with newly diagnosed AML in a dose-dependent fashion. Taken together, our data showing that resveratrol is an effective in vitro inhibitor of AML cells suggest that this compound may have a role in future therapies for AML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Marcucci, M. D. Radmacher, K. Maharry, K. Mrozek, A. S. Ruppert, P. Paschka, T. Vukosavljevic, S. P. Whitman, C. D. Baldus, C. Langer, et al. 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