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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5112-5121. Prepublished online as a Blood First Edition Paper on March 1, 2007; DOI 10.1182/blood-2007-01-067256. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-067256v1 109/12/5112    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kunnumakkara, A. B Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Kunnumakkara, A. B Articles by Aggarwal, B. B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 10, 2007 Accepted February 26, 2007 Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1 mediated NF-B activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis Ajaikumar B Kunnumakkara, Asha S Nair, Kwang Seok Ahn, Manoj K Pandey, Zhengfang Yi, Mingyao Liu, and Bharat B. Aggarwal* Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University System HSC, Houston, Texas, United States * Corresponding author; email: aggarwal{at}mdanderson.org. Gossypin, a flavone originally isolated from Hibiscus vitifolius, has been shown to suppress angiogenesis, inflammation and carcinogenesis. However, the mechanisms of these activities are unknown. Because nuclear factor-B (NF-B) is associated with inflammation, carcinogenesis, hyperproliferation, invasion and angiogenesis, we hypothesized that gossypin mediates its effects through modulation of NF-B activation. In the present study we demonstrate that gossypin (and not gossypetin, an aglycone analogue) inhibited NF-B activation induced by inflammatory stimuli and carcinogens. Constitutive NF-B activation in tumor cells was also inhibited by this flavone. Inhibition of IB kinase by gossypin led to the suppression of IB phosphorylation and degradation, p65 nuclear translocation and NF-B-regulated gene expression. This, in turn, led to the downregulation of gene products involved in cell survival (IAP2, XIAP, Bcl-2, Bcl-xL, survivin, and FLIP), proliferation (c-myc, cyclin D1 and cyclooxygenase-2), angiogenesis (VEGF) and invasion (MMP-9). Suppression of these gene products by gossypin enhanced apoptosis induced by TNF and chemotherapeutic agents, suppressed TNF-induced cellular invasion, abrogated receptor activator of NF-B ligand-induced osteoclastogenesis and VEGF induced migration of HUVEC. Overall, our results demonstrate that gossypin inhibits the NF-B activation pathway, which may explain its role in the suppression of inflammation, carcinogenesis and angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020