SEARCH:   Advanced

Blood, 15 November 2006, Vol. 108, No. 10, pp. 3441-3449. Prepublished online as a Blood First Edition Paper on June 13, 2006; DOI 10.1182/blood-2006-04-016055. This Article Full Text Full Text (PDF) Erratum (v109,p10) All Versions of this Article: blood-2006-04-016055v1 blood-2006-04-016055v2 108/10/3441    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 Catley, L. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Catley, L. Articles by Anderson, K. C. Related Collections Neoplasia Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Aggresome induction by proteasome inhibitor bortezomib and -tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells Laurence Catley, Ellen Weisberg, Tanyel Kiziltepe, Yu-Tzu Tai, Teru Hideshima, Paola Neri, Pierfrancesco Tassone, Peter Atadja, Dharminder Chauhan, Nikhil C. Munshi, and Kenneth C. Anderson From the Department of Medical Oncology, Dana-Farber Cancer Institute, and the Department of Medicine, Harvard Medical School, Boston, MA; the VA Hospital, Boston, MA; and the Novartis Institutes for Biomedical Research, Oncology Research, East Hanover, NJ. Histone deacetylase (HDAC) inhibitors have shown cytotoxicity as single agents in preclinical studies for multiple myeloma (MM) cells. LBH589 is a novel hydroxamic acid derivative that at low nanomolar concentrations induces apoptosis in MM cells resistant to conventional therapies via caspase activation and poly-(ADP-ribose) polymerase (PARP) cleavage. Significant synergistic cytotoxicity was observed with LBH589 in combination with bortezomib against MM cells that were sensitive and resistant to dexamethasone (Dex), as well as primary patient MM cells. LBH589 at low nanomolar concentrations also induced -tubulin hyperacetylation. Aggresome formation was observed in the presence of bortezomib, and the combination of LBH589 plus bortezomib induced the formation of abnormal bundles of hyeracetylated -tubulin but with diminished aggresome size and apoptotic nuclei. These data confirm the potential clinical benefit of combining HDAC inhibitors with proteasome inhibitors, and provide insight into the mechanisms of synergistic anti-MM activity of bortezomib in combination with LBH589. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Badros, A. M. Burger, S. Philip, R. Niesvizky, S. S. Kolla, O. Goloubeva, C. Harris, J. Zwiebel, J. J. Wright, I. Espinoza-Delgado, et al. Phase I Study of Vorinostat in Combination with Bortezomib for Relapsed and Refractory Multiple Myeloma Clin. Cancer Res., August 15, 2009; 15(16): 5250 - 5257. [Abstract] [Full Text] [PDF] S. Deleu, M. Lemaire, J. Arts, E. Menu, E. Van Valckenborgh, I. Vande Broek, H. De Raeve, L. Coulton, B. Van Camp, P. Croucher, et al. Bortezomib Alone or in Combination with the Histone Deacetylase Inhibitor JNJ-26481585: Effect on Myeloma Bone Disease in the 5T2MM Murine Model of Myeloma Cancer Res., July 1, 2009; 69(13): 5307 - 5311. [Abstract] [Full Text] [PDF] B. Hoang, A. Benavides, Y. Shi, P. Frost, and A. Lichtenstein Effect of autophagy on multiple myeloma cell viability Mol. Cancer Ther., July 1, 2009; 8(7): 1974 - 1984. [Abstract] [Full Text] [PDF] H. M. Prince, M. J. Bishton, and S. J. Harrison Clinical Studies of Histone Deacetylase Inhibitors Clin. Cancer Res., June 15, 2009; 15(12): 3958 - 3969. [Abstract] [Full Text] [PDF] R. L. Piekarz and S. E. Bates Epigenetic Modifiers: Basic Understanding and Clinical Development Clin. Cancer Res., June 15, 2009; 15(12): 3918 - 3926. [Abstract] [Full Text] [PDF] L. Ellis, Y. Pan, G. K. Smyth, D. J. George, C. McCormack, R. Williams-Truax, M. Mita, J. Beck, H. Burris, G. Ryan, et al. Histone Deacetylase Inhibitor Panobinostat Induces Clinical Responses with Associated Alterations in Gene Expression Profiles in Cutaneous T-Cell Lymphoma Clin. Cancer Res., July 15, 2008; 14(14): 4500 - 4510. [Abstract] [Full Text] [PDF] M. Kraus, E. Malenke, J. Gogel, H. Muller, T. Ruckrich, H. Overkleeft, H. Ovaa, E. Koscielniak, J. T. Hartmann, and C. Driessen Ritonavir induces endoplasmic reticulum stress and sensitizes sarcoma cells toward bortezomib-induced apoptosis Mol. Cancer Ther., July 1, 2008; 7(7): 1940 - 1948. [Abstract] [Full Text] [PDF] E. De Bruyne, T. J. Bos, K. Asosingh, I. Vande Broek, E. Menu, E. Van Valckenborgh, P. Atadja, V. Coiteux, X. Leleu, K. Thielemans, et al. Epigenetic Silencing of the Tetraspanin CD9 during Disease Progression in Multiple Myeloma Cells and Correlation with Survival Clin. Cancer Res., May 15, 2008; 14(10): 2918 - 2926. [Abstract] [Full Text] [PDF] A. Scuto, M. Kirschbaum, C. Kowolik, L. Kretzner, A. Juhasz, P. Atadja, V. Pullarkat, R. Bhatia, S. Forman, Y. Yen, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells Blood, May 15, 2008; 111(10): 5093 - 5100. [Abstract] [Full Text] [PDF] C. A. Hassig, K. T. Symons, X. Guo, P.-M. Nguyen, T. Annable, P. L. Wash, J. E. Payne, D. A. Jenkins, C. Bonnefous, C. Trotter, et al. KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo Mol. Cancer Ther., May 1, 2008; 7(5): 1054 - 1065. [Abstract] [Full Text] [PDF] Y. Dai, S. Chen, L. B. Kramer, V. L. Funk, P. Dent, and S. Grant Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells Clin. Cancer Res., January 15, 2008; 14(2): 549 - 558. [Abstract] [Full Text] [PDF] C. Yu, B. B. Friday, L. Yang, P. Atadja, D. Wigle, J. Sarkaria, and A. A. Adjei Mitochondrial Bax translocation partially mediates synergistic cytotoxicity between histone deacetylase inhibitors and proteasome inhibitors in glioma cells Neuro-oncol, January 1, 2008; 10(3): 309 - 319. [Abstract] [Full Text] [PDF] C. Yu, B. B. Friday, J.-P. Lai, A. McCollum, P. Atadja, L. R. Roberts, and A. A. Adjei Abrogation of MAPK and Akt Signaling by AEE788 Synergistically Potentiates Histone Deacetylase Inhibitor-Induced Apoptosis through Reactive Oxygen Species Generation Clin. Cancer Res., February 15, 2007; 13(4): 1140 - 1148. [Abstract] [Full Text] [PDF] S. Trudel, A. K. Stewart, Z. Li, Y. Shu, S.-B. Liang, Y. Trieu, D. Reece, J. Paterson, D. Wang, and X.-Y. Wen The Bcl-2 Family Protein Inhibitor, ABT-737, Has Substantial Antimyeloma Activity and Shows Synergistic Effect with Dexamethasone and Melphalan Clin. Cancer Res., January 15, 2007; 13(2): 621 - 629. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020