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Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-04-1154. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-04-1154v1 102/3/1028    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 Mathas, S. Articles by Dörken, B. Search for Related Content PubMed PubMed Citation Articles by Mathas, S. Articles by Dörken, B. Related Collections Apoptosis Signal Transduction Chemokines, Cytokines, and Interleukins Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 1028-1034 NEOPLASIA Inhibition of NF-B essentially contributes to arsenic-induced apoptosis Stephan Mathas, Andreas Lietz, Martin Janz, Michael Hinz, Franziska Jundt, Claus Scheidereit, Kurt Bommert, and Bernd Dörken From the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; and Humboldt University, Charité, Robert-Rössle-Klinik, Berlin, Germany Arsenic can induce apoptosis and is an efficient drug for the treatment of acute promyelocytic leukemia. Currently, clinical studies are investigating arsenic as a therapeutic agent for a variety of malignancies. In this study, Hodgkin/Reed-Sternberg (HRS) cell lines served as model systems to characterize the role of nuclear factor–B (NF-B) in arsenic-induced apoptosis. Arsenic rapidly down-regulated constitutive IB kinase (IKK) as well as NF-B activity and induced apoptosis in HRS cell lines containing functional IB proteins. In these cell lines, apoptosis was blocked by inhibition of caspase-8 and caspase-3–like activity. Furthermore, arsenic treatment down-regulated NF-B target genes, including tumor necrosis factor-receptor–associated factor 1 (TRAF1), c-IAP2, interleukin-13 (IL-13), and CCR7. In contrast, cell lines with mutated, functionally inactive IB proteins or with a weak constitutive IKK/NF-B activity showed no alteration of the NF-B activity and were resistant to arsenic-induced apoptosis. A direct role of the NF-B pathway in arsenic-induced apoptosis is shown by transient overexpression of NF-B–p65 in L540Cy HRS cells, which protected the cells from arsenic-induced apoptosis. In addition, treatment of NOD/SCID mice with arsenic trioxide induced a dramatic reduction of xenotransplanted L540Cy Hodgkin tumors concomitant with NF-B inhibition. We conclude that inhibition of NF-B contributes to arsenic-induced apoptosis. Furthermore, pharmacologic inhibition of the IKK/NF-B activity might be a powerful treatment option for Hodgkin lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Dolniak, E. Katsoulidis, N. Carayol, J. K. Altman, A. J. Redig, M. S. Tallman, T. Ueda, R. Watanabe-Fukunaga, R. Fukunaga, and L. C. Platanias Regulation of Arsenic Trioxide-induced Cellular Responses by Mnk1 and Mnk2 J. Biol. Chem., May 2, 2008; 283(18): 12034 - 12042. [Abstract] [Full Text] [PDF] J. Wang, R. R. Seethala, Q. Zhang, W. Gooding, C. van Waes, H. Hasegawa, and R. L. 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