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Blood, 26 February 2009, Vol. 113, No. 9, pp. 2003-2013. Prepublished online as a Blood First Edition Paper on October 24, 2008; DOI 10.1182/blood-2008-04-151944. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-04-151944v1 113/9/2003    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 Harikumar, K. B. Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Harikumar, K. B. Articles by Aggarwal, B. B. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Modification of the cysteine residues in IB kinase and NF-B (p65) by xanthohumol leads to suppression of NF-B–regulated gene products and potentiation of apoptosis in leukemia cells Kuzhuvelil B. Harikumar1, Ajaikumar B. Kunnumakkara1, Kwang S. Ahn1, Preetha Anand1, Sunil Krishnan2, Sushovan Guha3, and Bharat B. Aggarwal1 1 Cytokine Research Laboratory, Department of Experimental Therapeutics, 2 Department of Radiation Oncology, and 3 Department of Gastroenterology, Hepatology and Nutrition, University of Texas M. D. Anderson Cancer Center, Houston Xanthohumol (XN), a prenylated chalcone isolated from hop plant, exhibits anti-inflammatory, antiproliferative, and antiangiogenic properties through an undefined mechanism. Whether examined by intracellular esterase activity, phosphatidylserine externalization, DNA strand breaks, or caspase activation, we found that XN potentiated tumor necrosis factor–induced apoptosis in leukemia and myeloma cells. This enhancement of apoptosis correlated with down-regulation of nuclear factor-B (NF-B) survivin, bcl-xL, XIAP, cIAP1, cIAP2, cylin D1, and c-myc. XN down-regulated both constitutive and inducible NF-B activation, inhibition of phosphorylation and degradation of IB, suppression of p65 nuclear translocation, and NF-B–dependent reporter gene transcription. XN directly inhibited tumor necrosis factor-induced IB kinase (IKK) activation and a reducing agent abolished this inhibition, indicating the role of cysteine residue. XN had no effect on the IKK activity when cysteine residue 179 of IKK was mutated to alanine. XN also directly inhibited binding of p65 to DNA, a reducing agent reversed this effect, and mutation of cysteine residue 38 to serine of p65 abolished this effect. Thus, our results show that modification of cysteine residues of IKK and p65 by XN leads to inhibition of the NF-B activation pathway, suppression of antiapoptotic gene products, and potentiation of apoptosis in leukemia cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. LUST, B. VANHOECKE, M. VAN GELE, J. BOELENS, H. VAN MELCKEBEKE, M. KAILEH, W. VANDEN BERGHE, G. HAEGEMAN, J. PHILIPPE, M. BRACKE, et al. Xanthohumol Activates the Proapoptotic Arm of the Unfolded Protein Response in Chronic Lymphocytic Leukemia Anticancer Res, October 1, 2009; 29(10): 3797 - 3805. [Abstract] [Full Text] [PDF]

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