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Blood, 15 July 2005, Vol. 106, No. 2, pp. 641-649. Prepublished online as a Blood First Edition Paper on April 5, 2005; DOI 10.1182/blood-2004-12-4589. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4589v1 106/2/641    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 Takada, Y. Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Takada, Y. Articles by Aggarwal, B. B. Related Collections Immunobiology Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Indole-3-carbinol suppresses NF-B and IB kinase activation, causing inhibition of expression of NF-B-regulated antiapoptotic and metastatic gene products and enhancement of apoptosis in myeloid and leukemia cells Yasunari Takada, Michael Andreeff, and Bharat B. Aggarwal From the Cytokine Research Laboratory, Department of Experimental Therapeutics, and the Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston. Indole-3-carbinol, found in Brassica species vegetables (such as cabbage, cauliflower, and brussels spouts), exhibits antitumor effects through poorly defined mechanisms. Because several genes that regulate apoptosis, proliferation, and metastasis are regulated by nuclear factor-B (NF-B), we postulated that indole-3-carbinol must mediate its activity through NF-B modulation. We demonstrated that indole-3-carbinol suppressed constitutive NF-B activation and activation induced by tumor necrosis factor (TNF), interleukin-1 (IL-1), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and cigarette smoke; the suppression was not cell type specific, because activation was inhibited in myeloid, leukemia, and epithelial cells. This activation correlated with the sequential suppression of the IB kinase, IB phosphorylation, IB ubiquitination, IB degradation, p65 phosphorylation, p65 nuclear translocation, p65 acetylation, and NF-B-dependent reporter gene expression. The NF-B-regulated gene products cyclin D1, cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), survivin, inhibitor-of-apoptosis protein-1 (IAP1), IAP2, X chromosome-linked IAP (XIAP), Bcl-2, Bfl-1/A1, TNF receptor-associated factor-1 (TRAF1), and Fas-associated death domain protein-like interleukin-1-converting enzyme inhibitory protein (FLIP) were all down-regulated by indole-3-carbinol. This down-regulation led to the potentiation of apoptosis induced by cytokines and chemotherapeutic agents. Indole-3-carbinol suppressed constitutive NF-B activation in mononuclear cells derived from bone marrow of acute myelogenous leukemia patients, and this correlated with inhibition of cell growth. Overall, our results indicated that indole-3-carbinol inhibits NF-B and NF-B-regulated gene expression and that this mechanism may provide the molecular basis for its ability to suppress tumorigenesis. 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