SEARCH:   Advanced

Blood, 1 May 2004, Vol. 103, No. 9, pp. 3496-3502. Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-05-1412. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1412v1 103/9/3496    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 Davison, K. Articles by Miller, W. H. Search for Related Content PubMed PubMed Citation Articles by Davison, K. Articles by Miller, W. H., Jr Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA JNK activation is a mediator of arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells Kelly Davison, Koren K. Mann, Samuel Waxman, and Wilson H. Miller, Jr From the Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montréal, Québec, Canada, and Mount Sinai School of Medicine, New York, NY. Arsenic trioxide induces c-jun N-terminal kinase (JNK) activation and apoptosis in acute promyelocytic leukemia (APL), where it has major clinical activity, but whether JNK is necessary to induce apoptosis is unknown. To clarify this necessity, we established 2 arsenic trioxide (As2O3)-resistant subclones of the APL cell line, NB4. Both resistant lines showed little activation of JNK1 following treatment with As2O3, even at doses sufficient to elicit robust activation in NB4 cells. One mechanism of resistance in these cells is up-regulated glutathione (GSH) content, and GSH depletion by L-buthionine-[S,R]-sulfoximine (BSO) restores JNK activation and As2O3 sensitivity. This correlation between JNK activation and apoptosis led us to test whether inhibition of JNK would protect cells from As2O3-induced apoptosis. SEK1-/- mouse embryo fibroblasts (MEFs) showed diminished JNK activation following As2O3 treatment and were protected from As2O3-induced but not doxorubicin-induced apoptosis. Furthermore, treatment of arsenic trioxide-sensitive APL cells with the JNK inhibitor, dicumarol, significantly increased growth and survival in response to As2O3 but did not protect cells from doxorubicin. Together, these data support an essential role for JNK signaling in the induction of growth inhibition and apoptosis by As2O3 and suggest that activating JNK may provide a therapeutic advantage in the treatment of cancers that do not respond to arsenic alone. (Blood. 2004;103:3496-3502) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. K. Mann, M. Colombo, and W. H. Miller Jr. Arsenic trioxide decreases AKT protein in a caspase-dependent manner Mol. Cancer Ther., June 1, 2008; 7(6): 1680 - 1687. [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. K. Altman, P. Yoon, E. Katsoulidis, B. Kroczynska, A. Sassano, A. J. Redig, H. Glaser, A. Jordan, M. S. Tallman, N. Hay, et al. Regulatory Effects of Mammalian Target of Rapamycin-mediated Signals in the Generation of Arsenic Trioxide Responses J. Biol. Chem., January 25, 2008; 283(4): 1992 - 2001. [Abstract] [Full Text] [PDF] E. Fox, B. I. Razzouk, B. C. Widemann, S. Xiao, M. O'Brien, W. Goodspeed, G. H. Reaman, S. M. Blaney, A. J. Murgo, F. M. Balis, et al. Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma Blood, January 15, 2008; 111(2): 566 - 573. [Abstract] [Full Text] [PDF] D. Hamilton, J. H. Wu, and G. Batist Structure-Based Identification of Novel Human {gamma}-Glutamylcysteine Synthetase Inhibitors Mol. Pharmacol., April 1, 2007; 71(4): 1140 - 1147. [Abstract] [Full Text] [PDF] D. Chen, R. Chan, S. Waxman, and Y. Jing Buthionine Sulfoximine Enhancement of Arsenic Trioxide-Induced Apoptosis in Leukemia and Lymphoma Cells Is Mediated via Activation of c-Jun NH2-Terminal Kinase and Up-regulation of Death Receptors Cancer Res., December 1, 2006; 66(23): 11416 - 11423. [Abstract] [Full Text] [PDF] D. Zhang, L. Song, J. Li, K. Wu, and C. Huang Coordination of JNK1 and JNK2 Is Critical for GADD45{alpha} Induction and Its Mediated Cell Apoptosis in Arsenite Responses J. Biol. Chem., November 10, 2006; 281(45): 34113 - 34123. [Abstract] [Full Text] [PDF] Y. Joe, J.-H. Jeong, S. Yang, H. Kang, N. Motoyama, P. P. Pandolfi, J. H. Chung, and M. K. Kim ATR, PML, and CHK2 Play a Role in Arsenic Trioxide-induced Apoptosis J. Biol. Chem., September 29, 2006; 281(39): 28764 - 28771. [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] N. Giafis, E. Katsoulidis, A. Sassano, M. S. Tallman, L. S. Higgins, A. R. Nebreda, R. J. Davis, and L. C. Platanias Role of the p38 Mitogen-Activated Protein Kinase Pathway in the Generation of Arsenic Trioxide-Dependent Cellular Responses. Cancer Res., July 1, 2006; 66(13): 6763 - 6771. [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] S. Kann, C. Estes, J. F. Reichard, M.-y. Huang, M. A. Sartor, S. Schwemberger, Y. Chen, T. P. Dalton, H. G. Shertzer, Y. Xia, et al. Butylhydroquinone Protects Cells Genetically Deficient in Glutathione Biosynthesis from Arsenite-Induced Apoptosis Without Significantly Changing Their Prooxidant Status Toxicol. Sci., October 1, 2005; 87(2): 365 - 384. [Abstract] [Full Text] [PDF] Z. Diaz, M. Colombo, K. K. Mann, H. Su, K. N. Smith, D. S. Bohle, H. M. Schipper, and W. H. Miller Jr Trolox selectively enhances arsenic-mediated oxidative stress and apoptosis in APL and other malignant cell lines Blood, February 1, 2005; 105(3): 1237 - 1245. [Abstract] [Full Text] [PDF] O. Sordet, Z. Liao, H. Liu, S. Antony, E. V. Stevens, G. Kohlhagen, H. Fu, and Y. Pommier Topoisomerase I-DNA Complexes Contribute to Arsenic Trioxide-induced Apoptosis J. Biol. Chem., August 6, 2004; 279(32): 33968 - 33975. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020