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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2286-2295. Prepublished online as a Blood First Edition Paper on August 1, 2007; DOI 10.1182/blood-2007-04-084996. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-04-084996v1 blood-2007-04-084996v2 110/7/2286    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 Ahn, K. S. Articles by Aggarwal, B. B. Search for Related Content PubMed PubMed Citation Articles by Ahn, K. S. Articles by Aggarwal, B. B. Related Collections Hematopoiesis and Stem Cells Apoptosis Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS Salinosporamide A (NPI-0052) potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through down-modulation of NF-B–regulated gene products Kwang Seok Ahn1, Gautam Sethi1, Ta-Hsiang Chao2, Saskia T. C. Neuteboom2, Madan M. Chaturvedi1,3, Michael A. Palladino2, Anas Younes4, and Bharat B. Aggarwal1 1 Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston; 2 Nereus Pharmaceuticals, San Diego, CA; 3 Department of Zoology, University of Delhi, Delhi, India, and 4 Department of Lymphoma/Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston Salinosporamide A (also called NPI-0052), recently identified from the marine bacterium Salinispora tropica, is a potent inhibitor of 20S proteasome and exhibits therapeutic potential against a wide variety of tumors through a poorly understood mechanism. Here we demonstrate that salinosporamide A potentiated the apoptosis induced by tumor necrosis factor (TNF), bortezomib, and thalidomide, and this correlated with down-regulation of gene products that mediate cell proliferation (cyclin D1, cyclooxygenase-2 [COX-2], and c-Myc), cell survival (Bcl-2, Bcl-xL, cFLIP, TRAF1, IAP1, IAP2, and survivin), invasion (matrix metallopro-teinase-9 [MMP-9] and ICAM-1), and angiogenesis (vascular endothelial growth factor [VEGF]). Salinosporamide A also suppressed TNF-induced tumor cell invasion and receptor activator of nuclear factor B ligand (RANKL)-induced osteoclastogenesis. We also found that it suppressed both constitutive and inducible NF-B activation. Compared with bortezomib, MG-132, N-acetyl-leucyl-leucyl-norleucinal (ALLN), and lactacystin, salinosporamide A was found to be the most potent suppressor of NF-B activation. Further studies showed that salinosporamide A inhibited TNF-induced inhibitory subunit of NF-B (IB) degradation, nuclear translocation of p65, and NF-B-dependent reporter gene expression but had no effect on IB kinase activation, IB phosphorylation, or IB ubiquitination. Thus, overall, our results indicate that salinosporamide A enhances apoptosis, suppresses osteoclastogenesis, and inhibits invasion through suppression of the NF-B pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. B. Aggarwal, R.V. Vijayalekshmi, and B. Sung Targeting Inflammatory Pathways for Prevention and Therapy of Cancer: Short-Term Friend, Long-Term Foe Clin. Cancer Res., January 15, 2009; 15(2): 425 - 430. [Abstract] [Full Text] [PDF] S. Baritaki, E. Suzuki, K. Umezawa, D. A. Spandidos, J. Berenson, T. R. Daniels, M. L. Penichet, A. R. Jazirehi, M. Palladino, and B. Bonavida Inhibition of Yin Yang 1-Dependent Repressor Activity of DR5 Transcription and Expression by the Novel Proteasome Inhibitor NPI-0052 Contributes to its TRAIL-Enhanced Apoptosis in Cancer Cells J. Immunol., May 1, 2008; 180(9): 6199 - 6210. [Abstract] [Full Text] [PDF]

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