SEARCH:   Advanced

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 Neoplasia Apoptosis Signal Transduction Chemokines, Cytokines, and Interleukins 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: K. Silbermann, G. Schneider, and R. Grassmann Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-{kappa}B and NFAT J. Gen. Virol., November 1, 2008; 89(11): 2788 - 2798. [Abstract] [Full Text] [PDF] 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. Ferris Autocrine and Paracrine Chemokine Receptor 7 Activation in Head and Neck Cancer: Implications for Therapy J Natl Cancer Inst, April 2, 2008; 100(7): 502 - 512. [Abstract] [Full Text] [PDF] B. H. Kim, E. Roh, H. Y. Lee, I.-J. Lee, B. Ahn, S.-H. Jung, H. Lee, S.-B. Han, and Y. Kim Benzoxathiole Derivative Blocks Lipopolysaccharide-Induced Nuclear Factor-{kappa}B Activation and Nuclear Factor-{kappa}B-Regulated Gene Transcription through Inactivating Inhibitory {kappa}B Kinase {beta} Mol. Pharmacol., April 1, 2008; 73(4): 1309 - 1318. [Abstract] [Full Text] [PDF] Z. Peng, L. Peng, Y. Fan, E. Zandi, H. G. Shertzer, and Y. Xia A Critical Role for I{kappa}B Kinase beta in Metallothionein-1 Expression and Protection against Arsenic Toxicity J. Biol. Chem., July 20, 2007; 282(29): 21487 - 21496. [Abstract] [Full Text] [PDF] P. J. Jost and J. Ruland Aberrant NF-{kappa}B signaling in lymphoma: mechanisms, consequences, and therapeutic implications Blood, April 1, 2007; 109(7): 2700 - 2707. [Abstract] [Full Text] [PDF] A. Ciucci, P. Gianferretti, R. Piva, T. Guyot, T. J. Snape, S. M. Roberts, and M. G. Santoro Induction of Apoptosis in Estrogen Receptor-Negative Breast Cancer Cells by Natural and Synthetic Cyclopentenones: Role of the I{kappa}B Kinase/Nuclear Factor-{kappa}B Pathway Mol. Pharmacol., November 1, 2006; 70(5): 1812 - 1821. [Abstract] [Full Text] [PDF] P. Kannan-Thulasiraman, E. Katsoulidis, M. S. Tallman, J. S. C. Arthur, and L. C. Platanias Activation of the Mitogen- and Stress-activated Kinase 1 by Arsenic Trioxide J. Biol. Chem., August 11, 2006; 281(32): 22446 - 22452. [Abstract] [Full Text] [PDF] L. Bernal-Mizrachi, C. M. Lovly, and L. Ratner The role of NF-{kappa}B-1 and NF-{kappa}B-2-mediated resistance to apoptosis in lymphomas PNAS, June 13, 2006; 103(24): 9220 - 9225. [Abstract] [Full Text] [PDF] G. J. Schiller, J. Slack, J. D. Hainsworth, J. Mason, M. Saleh, D. Rizzieri, D. Douer, and A. F. List Phase II Multicenter Study of Arsenic Trioxide in Patients With Myelodysplastic Syndromes J. Clin. Oncol., June 1, 2006; 24(16): 2456 - 2464. [Abstract] [Full Text] [PDF] J. Xie and Z. A. Shaikh Cadmium-Induced Apoptosis in Rat Kidney Epithelial Cells Involves Decrease in Nuclear Factor-Kappa B Activity Toxicol. Sci., May 1, 2006; 91(1): 299 - 308. [Abstract] [Full Text] [PDF] A. Lemarie, C. Morzadec, D. Merino, O. Micheau, O. Fardel, and L. Vernhet Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic Differentiation through Nuclear Factor-{kappa}B-Related Survival Pathway Down-Regulation J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 304 - 314. [Abstract] [Full Text] [PDF] R. K. Thomas, M. L. Sos, T. Zander, O. Mani, A. Popov, D. Berenbrinker, S. Smola-Hess, J. L. Schultze, and J. Wolf Inhibition of Nuclear Translocation of Nuclear Factor-{kappa}B Despite Lack of Functional I{kappa}B{alpha} Protein Overcomes Multiple Defects in Apoptosis Signaling in Human B-Cell Malignancies Clin. Cancer Res., November 15, 2005; 11(22): 8186 - 8194. [Abstract] [Full Text] [PDF] C.-L. Law, K. A. Gordon, J. Collier, K. Klussman, J. A. McEarchern, C. G. Cerveny, B. J. Mixan, W. P. Lee, Z. Lin, P. Valdez, et al. Preclinical Antilymphoma Activity of a Humanized Anti-CD40 Monoclonal Antibody, SGN-40 Cancer Res., September 15, 2005; 65(18): 8331 - 8338. [Abstract] [Full Text] [PDF] F. Jundt, N. Raetzel, C. Muller, C. F. Calkhoven, K. Kley, S. Mathas, A. Lietz, A. Leutz, and B. Dorken A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas Blood, September 1, 2005; 106(5): 1801 - 1807. [Abstract] [Full Text] [PDF] D. Re, R. K. Thomas, K. Behringer, and V. Diehl From Hodgkin disease to Hodgkin lymphoma: biologic insights and therapeutic potential Blood, June 15, 2005; 105(12): 4553 - 4560. [Abstract] [Full Text] [PDF] A. Rodriguez, N. Martinez, F. I. Camacho, E. Ruiz-Ballesteros, P. Algara, J.-F. Garcia, J. Menarguez, T. Alvaro, M. F. Fresno, F. Solano, et al. Variability in the Degree of Expression of Phosphorylated I{kappa}B{alpha} in Chronic Lymphocytic Leukemia Cases With Nodal Involvement Clin. Cancer Res., October 15, 2004; 10(20): 6796 - 6806. [Abstract] [Full Text] [PDF] P. Lunghi, A. Costanzo, M. Levrero, and A. Bonati Treatment with arsenic trioxide (ATO) and MEK1 inhibitor activates the p73-p53AIP1 apoptotic pathway in leukemia cells Blood, July 15, 2004; 104(2): 519 - 525. [Abstract] [Full Text] [PDF] V. N. Ivanov and T. K. Hei Arsenite Sensitizes Human Melanomas to Apoptosis via Tumor Necrosis Factor {alpha}-mediated Pathway J. Biol. Chem., May 21, 2004; 279(21): 22747 - 22758. [Abstract] [Full Text] [PDF] Y. Dai, X.-Y. Pei, M. Rahmani, D. H. Conrad, P. Dent, and S. Grant Interruption of the NF-{kappa}B pathway by Bay 11-7082 promotes UCN-01-mediated mitochondrial dysfunction and apoptosis in human multiple myeloma cells Blood, April 1, 2004; 103(7): 2761 - 2770. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020