|
|
Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-04-1154.
Submitted April 16, 2002
Accepted March 25, 2003
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 Doerken
Max-Delbruck-Center for Molecular Medicine, Berlin, Germany; Charite, Robert-Rossle-Klinik, Humbolt University, Berlin, Germany
* Corresponding author; email: mathas{at}rrk-berlin.de.
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 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 could be blocked by inhibition of caspase-8 and caspase-3 like activity. Furthermore, arsenic treatment down-regulated NF-B target genes, including TRAF1, c-IAP2, 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, pharmacological inhibition of the IKK/NF-B activity might be a powerful treatment option for Hodgkin's 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]
|
|
|
|
|
