This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hu, X. Articles by Zuckerman, K. S. Search for Related Content PubMed PubMed Citation Articles by Hu, X. Articles by Zuckerman, K. S.

An IB Inhibitor Causes Leukemia Cell Death through a p38 MAP Kinase-dependent, NF-B-independent Mechanism

Interdisciplinary Oncology Program [X. H., W. E. J., L. C. M., M. B., A. D., N. R-Z., B. A. B., K. S. Z.] and Departments of Pathology [W. E. J., L. C. M.], Internal Medicine [K. S. Z.], and Biochemistry and Molecular Biology [K. S. Z.], University of South Florida, and the H. Lee Moffitt Cancer Center, Tampa, Florida 33612 [X. H., W. E. J., L. C. M., M. B., A. D., N. R-Z., B. A. B., K. S. Z.]

Treatment of U937 cells with an IB phosphorylation inhibitor, Bay 11-7085, induced a rapid phosphorylation of p38 mitogen-activated protein (MAP) kinase, significant apoptosis, extensive necrosis, and a weak phosphorylation of MAP kinase kinase. Bay 11-7085 had no effect on the basal levels of phosphorylated IB but completely inhibited phorbol 12-myristate 13-acetate-induced phosphorylation of IB. Although Bay 11-7085 prevented phorbol 12-myristate 13-acetate-induced NF-B nuclear translocation, SN50, a specific inhibitor of nuclear translocation and function of NF-B, did not induce any significant nuclear/DNA fragmentation, caspase 3 activation, or cell death. The p38 MAP kinase-specific inhibitor, SB203580, completely inhibited the phosphorylation of p38 MAP kinase and significantly decreased Bay 11-7085-induced apoptosis. In contrast, the MAP kinase kinase-specific inhibitor PD98059 had no effect on Bay 11-7085-induced apoptosis. Caspase-specific inhibitor, z-Val-Ala-Asp-fluoromethyl ketone prevented Bay 11-7085-induced activation of caspase 3 but was not able to block Bay 11-7085-induced phosphorylation of p38 MAP kinase. These data suggest that Bay 11-7085 induces apoptosis through a p38 MAP kinase-dependent, NF-B-independent mechanism.

This article has been cited by other articles:

				R. G. Uzzo, P. L. Crispen, K. Golovine, P. Makhov, E. M. Horwitz, and V. M. Kolenko Diverse effects of zinc on NF-{kappa}B and AP-1 transcription factors: implications for prostate cancer progression Carcinogenesis, October 1, 2006; 27(10): 1980 - 1990. [Abstract] [Full Text] [PDF]

				H. Yang, M. Bocchetta, B. Kroczynska, A. G. Elmishad, Y. Chen, Z. Liu, C. Bubici, B. T. Mossman, H. I. Pass, J. R. Testa, et al. TNF-{alpha} inhibits asbestos-induced cytotoxicity via a NF-{kappa}B-dependent pathway, a possible mechanism for asbestos-induced oncogenesis PNAS, July 5, 2006; 103(27): 10397 - 10402. [Abstract] [Full Text] [PDF]

				M.-T. Ling, X. Wang, D. T. Lee, P.C. Tam, S.-W. Tsao, and Y.-C. Wong Id-1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R) Carcinogenesis, April 1, 2004; 25(4): 517 - 525. [Abstract] [Full Text] [PDF]

				M. H. Ma, H. H. Yang, K. Parker, S. Manyak, J. M. Friedman, C. Altamirano, Z.-q. Wu, M. J. Borad, M. Frantzen, E. Roussos, et al. The Proteasome Inhibitor PS-341 Markedly Enhances Sensitivity of Multiple Myeloma Tumor Cells to Chemotherapeutic Agents Clin. Cancer Res., March 1, 2003; 9(3): 1136 - 1144. [Abstract] [Full Text] [PDF]

				X. Hu, M. Bryington, A. B. Fisher, X. Liang, X. Zhang, D. Cui, I. Datta, and K. S. Zuckerman Ubiquitin/Proteasome-dependent Degradation of D-type Cyclins Is Linked to Tumor Necrosis Factor-induced Cell Cycle Arrest J. Biol. Chem., May 3, 2002; 277(19): 16528 - 16537. [Abstract] [Full Text] [PDF]