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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 2, 2004 Accepted March 29, 2005 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* Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA * Corresponding author; email: aggarwal{at}mdanderson.org. Indole-3-carbinol, found in Brassica sp. 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 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 TNF, IL-1, PMA, LPS, and cigarette smoke; the suppression was not cell type specific, as 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, and p65 acetylation and with NF-B-dependent reporter gene expression. The NF-B-regulated gene products cyclin D1, COX-2, MMP-9, survivin, IAP1, IAP2, XIAP, Bcl-2, Bfl-1/A1, TRAF1, and FLIP were all downregulated by indole-3-carbinol. This downregulation 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. S. Khwaja, S. Wynne, I. Posey, and D. Djakiew 3,3'-Diindolylmethane Induction of p75NTR-Dependent Cell Death via the p38 Mitogen-Activated Protein Kinase Pathway in Prostate Cancer Cells Cancer Prevention Research, June 1, 2009; 2(6): 566 - 571. [Abstract] [Full Text] [PDF] J. O. Ban, J. H. Oh, B. Y. Hwang, D. C. Moon, H.-S. Jeong, S. Lee, S. Kim, H. Lee, K.-B. Kim, S. B. Han, et al. 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