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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3982-3988. Prepublished online as a Blood First Edition Paper on December 21, 2006; DOI 10.1182/blood-2006-10-053959. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-10-053959v1 109/9/3982    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 Kashkar, H. Articles by Krönke, M. Search for Related Content PubMed PubMed Citation Articles by Kashkar, H. Articles by Krönke, M. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA NF-B–independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs Hamid Kashkar1,2, Anke Deggerich1, Jens-Michael Seeger1, Benjamin Yazdanpanah1, Katja Wiegmann1, Dirk Haubert1, Carola Pongratz1, and Martin Krönke1,2 1 Institute for Medical Microbiology, Immunology and Hygiene and 2 the Center for Molecular Medicine Cologne, University of Cologne, Germany The proteasome inhibitor bortezomib has been shown to possess promising antitumor activity and significant efficacy against a variety of malignancies. Different studies demonstrated that bortezomib breaks the chemoresistance in different tumor cells basically by altering nuclear factor–B (NF-B) activity. NF-B has been shown to be constitutively active in most primary Hodgkin-Reed-Sternberg (H-RS) cells in lymph node sections and in Hodgkin lymphoma (HL) cell lines and was suggested to be a central molecular switch in apoptosis resistance in HL. Here we report a bimodal effect of bortezomib in HL cells. Whereas high-dose bortezomib induced direct cytotoxicity that correlated with decreased NF-B activity, low-dose bortezomib sensitized HL cells against a variety of cytotoxic drugs without altering NF-B action. Strikingly, bortezomib induced marked XIAP down-regulation at the posttranslational level that was independent of the NF-B status. Similarly, RNA interference (RNAi)–mediated XIAP down-regulation generated susceptibility to cytostatic agents. The results identify XIAP as an NF-B–independent target of bortezomib action that controls the chemoresistant phenotype of HL cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K.-F. Chen, P.-Y. Yeh, C. Hsu, C.-H. Hsu, Y.-S. Lu, H.-P. Hsieh, P.-J. Chen, and A.-L. Cheng Bortezomib Overcomes Tumor Necrosis Factor-related Apoptosis-inducing Ligand Resistance in Hepatocellular Carcinoma Cells in Part through the Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway J. Biol. Chem., April 24, 2009; 284(17): 11121 - 11133. [Abstract] [Full Text] [PDF] M. IIJIMA, I. MOMOSE, and D. IKEDA TP-110, a New Proteasome Inhibitor, Down-regulates IAPs in Human Multiple Myeloma Cells Anticancer Res, April 1, 2009; 29(4): 977 - 985. [Abstract] [Full Text] [PDF]

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