JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M009831200 on December 13, 2000

J. Biol. Chem., Vol. 276, Issue 11, 8029-8036, March 16, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/11/8029    most recent
M009831200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tabata, M.
Right arrow Articles by Ganapathi, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tabata, M.
Right arrow Articles by Ganapathi, R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Roles of NF-kappa B and 26 S Proteasome in Apoptotic Cell Death Induced by Topoisomerase I and II Poisons in Human Nonsmall Cell Lung Carcinoma*

Masahiro Tabata, Rika Tabata, Dale R. Grabowski, Ronald M. Bukowski, Mahrukh K. Ganapathi, and Ram GanapathiDagger

From the Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195

Activation of signaling pathways after DNA damage induced by topoisomerase (topo) poisons can lead to cell death by apoptosis. Treatment of human nonsmall cell lung carcinoma (NSCLC-3 or NSCLC-5) cells with the topo I poison SN-38 or the topo II poison etoposide (VP-16) leads to activation of NF-kappa B before induction of apoptosis. Inhibiting the degradation of Ikappa Balpha by pretreatment with the proteasome inhibitor MG-132 significantly inhibited NF-kappa B activation and apoptosis but not DNA damage induced by SN-38 or VP-16. Transfection of NSCLC-3 or NSCLC-5 cells with dominant negative mutant Ikappa Balpha (mIkappa Balpha ) inhibited SN-38 or VP-16 induced transcription and DNA binding activity of NF-kappa B without altering drug-induced apoptosis. Regulation of apoptosis by mitochondrial release of cytochrome c and activation of pro-caspase 9 followed by cleavage of poly(ADP-ribose) polymerase by effector caspases 3 and 7 was similar in neo and mIkappa Balpha cells treated with SN-38 or VP-16. In contrast to pretreatment with MG-132, exposure to MG-132 after SN-38 or VP-16 treatment of neo or mIkappa Balpha cells decreased cell cycle arrest in the S/G2 + M fraction and enhanced apoptosis compared with drug alone. In summary, apoptosis induced by topoisomerase poisons in NSCLC cells is not mediated by NF-kappa B but can be manipulated by proteasome inhibitors.

* This work was supported by United States Public Health Service Grants RO1 CA35531 and RO1 CA74939 and an educational/research grant from Rodney A. Beason, Medical Sciences Liaison Oncology, Medical Operations and Scientific Affairs, Pharmacia & Upjohn.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Taussig Cancer Center, R40, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. Tel.: 216-444-2085; Fax: 216-444-7115; E-mail: ganapar@ cc.ccf.org.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
A. G. Grozav, K. Chikamori, T. Kozuki, D. R. Grabowski, R. M. Bukowski, B. Willard, M. Kinter, A. H. Andersen, R. Ganapathi, and M. K. Ganapathi
Casein kinase I {delta}/{varepsilon} phosphorylates topoisomerase II{alpha} at serine-1106 and modulates DNA cleavage activity
Nucleic Acids Res., November 29, 2008; (2008) gkn934v1.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. W. Zmijewski, X. Zhao, Z. Xu, and E. Abraham
Exposure to hydrogen peroxide diminishes NF-{kappa}B activation, I{kappa}B-{alpha} degradation, and proteasome activity in neutrophils
Am J Physiol Cell Physiol, July 1, 2007; 293(1): C255 - C266.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Dolcet, D. Llobet, M. Encinas, J. Pallares, A. Cabero, J. A. Schoenenberger, J. X. Comella, and X. Matias-Guiu
Proteasome Inhibitors Induce Death but Activate NF-{kappa}B on Endometrial Carcinoma Cell Lines and Primary Culture Explants
J. Biol. Chem., August 4, 2006; 281(31): 22118 - 22130.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
D. Sohn, G. Totzke, F. Essmann, K. Schulze-Osthoff, B. Levkau, and R. U. Janicke
The proteasome is required for rapid initiation of death receptor-induced apoptosis.
Mol. Cell. Biol., March 1, 2006; 26(5): 1967 - 1978.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. A.J. Vaziri, J. Hill, K. Chikamori, D. R. Grabowski, N. Takigawa, M. Chawla-Sarkar, L. R. Rybicki, A. V. Gudkov, T. Mekhail, R. M. Bukowski, et al.
Sensitization of DNA damage-induced apoptosis by the proteasome inhibitor PS-341 is p53 dependent and involves target proteins 14-3-3{sigma} and survivin
Mol. Cancer Ther., December 1, 2005; 4(12): 1880 - 1890.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Jin, X. Liu, Z. Zhou, P. Yue, R. Lotan, F. R. Khuri, L. W.K. Chung, and S.-Y. Sun
Activation of Nuclear Factor-{kappa}B Contributes to Induction of Death Receptors and Apoptosis by the Synthetic Retinoid CD437 in DU145 Human Prostate Cancer Cells
Cancer Res., July 15, 2005; 65(14): 6354 - 6363.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Catley, Y.-T. Tai, R. Shringarpure, R. Burger, M. T. Son, K. Podar, P. Tassone, D. Chauhan, T. Hideshima, L. Denis, et al.
Proteasomal Degradation of Topoisomerase I Is Preceded by c-Jun NH2-Terminal Kinase Activation, Fas Up-Regulation, and Poly(ADP-Ribose) Polymerase Cleavage in SN38-Mediated Cytotoxicity against Multiple Myeloma
Cancer Res., December 1, 2004; 64(23): 8746 - 8753.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
Y. Xu and M. A. Villalona-Calero
Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity
Ann. Onc., December 1, 2002; 13(12): 1841 - 1851.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Bottero, V. Busuttil, A. Loubat, N. Magne, J.-L. Fischel, G. Milano, and J.-F. Peyron
Activation of Nuclear Factor {kappa}B through the IKK Complex by the Topoisomerase Poisons SN38 and Doxorubicin: A Brake to Apoptosis in HeLa Human Carcinoma Cells
Cancer Res., November 1, 2001; 61(21): 7785 - 7791.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Mao, S. D. Desai, C.-Y. Ting, J. Hwang, and L. F. Liu
26 S Proteasome-mediated Degradation of Topoisomerase II Cleavable Complexes
J. Biol. Chem., October 26, 2001; 276(44): 40652 - 40658.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K.-C. Huang, H. Gao, E. F. Yamasaki, D. R. Grabowski, S. Liu, L. L. Shen, K. K. Chan, R. Ganapathi, and R. M. Snapka
Topoisomerase II Poisoning by ICRF-193
J. Biol. Chem., November 21, 2001; 276(48): 44488 - 44494.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.