Table of Contents Author Guidelines Submit a Manuscript
Journal of Oncology
Volume 2011, Article ID 232037, 11 pages
http://dx.doi.org/10.1155/2011/232037
Research Article

Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101

1Division of Hematology/Oncology, Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
2Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
3Department of Biology, Clarion University, Clarion, PA 16214, USA
4Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA
5Department of Chemistry and Center for Chemical Methodologies and Library Development, University of Pittsburgh, Pittsburgh, PA 15260, USA

Received 21 May 2011; Accepted 18 July 2011

Academic Editor: Edward A. Copelan

Copyright © 2011 Marc J. Braunstein et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. W. Fewell, C. M. Smith, M. A. Lyon et al., “Small molecule modulators of endogenous and co-chaperone-stimulated Hsp70 ATPase activity,” Journal of Biological Chemistry, vol. 279, no. 49, pp. 51131–51140, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. S. V. Rajkumar, “Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management,” American Journal of Hematology, vol. 86, no. 1, pp. 57–65, 2011. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. B. Barlogie, R. A. Kyle, K. C. Anderson et al., “Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US intergroup trial S9321,” Journal of Clinical Oncology, vol. 24, no. 6, pp. 929–936, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. P. G. Richardson, E. Weller, S. Lonial et al., “Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma,” Blood, vol. 116, no. 5, pp. 679–686, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. P. L. Bergsagel and W. M. Kuehl, “Molecular pathogenesis and a consequent classification of multiple myeloma,” Journal of Clinical Oncology, vol. 23, no. 26, pp. 6333–6338, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. D. R. Carrasco, G. Tonon, Y. Huang et al., “High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients,” Cancer Cell, vol. 9, no. 4, pp. 313–325, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. T. Hideshima, C. Mitsiades, G. Tonon, P. G. Richardson, and K. C. Anderson, “Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets,” Nature Reviews Cancer, vol. 7, no. 8, pp. 585–598, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. A. M. Roccaro, T. Hideshima, N. Raje et al., “Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells,” Cancer Research, vol. 66, no. 1, pp. 184–191, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. S. V. Rajkumar, R. A. Mesa, R. Fonseca et al., “Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis,” Clinical Cancer Research, vol. 8, no. 7, pp. 2210–2216, 2002. View at Google Scholar · View at Scopus
  10. A. Vacca, R. Ria, F. Semeraro et al., “Endothelial cells in the bone marrow of patients with multiple myeloma,” Blood, vol. 102, no. 9, pp. 3340–3348, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. N. Mitsiades, C. S. Mitsiades, V. Poulaki et al., “Molecular sequelae of proteasome inhibition in human multiple myeloma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 22, pp. 14374–14379, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. A. H. Lee, N. N. Iwakoshi, K. C. Anderson, and L. H. Glimcher, “Proteasome inhibitors disrupt the unfolded protein response in myeloma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 17, pp. 9946–9951, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. J. J. Shah and R. Z. Orlowski, “Proteasome inhibitors in the treatment of multiple myeloma,” Leukemia, vol. 23, no. 11, pp. 1964–1979, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. L. Catley, E. Weisberg, T. Kiziltepe et al., “Aggresome induction by proteasome inhibitor bortezomib and α-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells,” Blood, vol. 108, no. 10, pp. 3441–3449, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. E. L. Davenport, H. E. Moore, A. S. Dunlop et al., “Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells,” Blood, vol. 110, no. 7, pp. 2641–2649, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. E. L. Davenport, A. Zeisig, L. I. Aronson et al., “Targeting heat shock protein 72 enhances Hsp90 inhibitor-induced apoptosis in myeloma,” Leukemia, vol. 24, no. 10, pp. 1804–1807, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. S. Meister, U. Schubert, K. Neubert et al., “Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition,” Cancer Research, vol. 67, no. 4, pp. 1783–1792, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. C. S. Mitsiades, N. S. Mitsiades, C. J. McMullan et al., “Antimyeloma activity of heat shock protein-90 inhibition,” Blood, vol. 107, no. 3, pp. 1092–1100, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. E. A. Obeng, L. M. Carlson, D. M. Gutman, W. J. Harrington Jr., K. P. Lee, and L. H. Boise, “Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells,” Blood, vol. 107, no. 12, pp. 4907–4916, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. P. G. Richardson, C. S. Mitsiades, J. P. Laubach, S. Lonial, A. A. Chanan-Khan, and K. C. Anderson, “Inhibition of heat shock protein 90 (HSP90) as a therapeutic strategy for the treatment of myeloma and other cancers,” British Journal of Haematology, vol. 152, no. 4, pp. 367–379, 2011. View at Publisher · View at Google Scholar · View at PubMed
  21. E. L. Davenport, A. Zeisig, L. I. Aronson et al., “Targeting heat shock protein 72 enhances Hsp90 inhibitor-induced apoptosis in myeloma,” Leukemia, vol. 24, no. 10, pp. 1804–1807, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. Y. Okawa, T. Hideshima, P. Steed et al., “SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK,” Blood, vol. 113, no. 4, pp. 846–855, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. A. Rodina, M. Vilenchik, K. Moulick et al., “Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer,” Nature Chemical Biology, vol. 3, no. 8, pp. 498–507, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. M. R. Knittler, S. Dirks, and I. G. Haas, “Molecular chaperones involved in protein degradation in the endoplasmic reticulum: quantitative interaction of the heat shock cognate protein BiP with partially folded immunoglobulin light chains that are degraded in the endoplasmic reticulum,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 5, pp. 1764–1768, 1995. View at Publisher · View at Google Scholar · View at Scopus
  25. N. C. Munshi, T. Hideshima, D. Carrasco et al., “Identification of genes modulated in multiple myeloma using genetically identical twin samples,” Blood, vol. 103, no. 5, pp. 1799–1806, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. R. Nimmanapalli, E. Gerbino, W. S. Dalton, V. Gandhi, and M. Alsina, “HSP70 inhibition reverses cell adhesion mediated and acquired drug resistance in multiple myeloma,” British Journal of Haematology, vol. 142, no. 4, pp. 551–561, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. A. Maloney and P. Workman, “HSP90 as a new therapeutic target for cancer therapy: the story unfolds,” Expert Opinion on Biological Therapy, vol. 2, no. 1, pp. 3–24, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. J. L. Brodsky and G. Chiosis, “Hsp70 molecular chaperones: emerging roles in human disease and identification of small molecule modulators,” Current Topics in Medicinal Chemistry, vol. 6, no. 11, pp. 1215–1225, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. S. K. Calderwood, “Heat shock proteins in breast cancer progression—a suitable case for treatment?” International Journal of Hyperthermia, vol. 26, no. 7, pp. 681–685, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. S. K. Calderwood, J. Gong, J. R. Theriault, S. S. Mambula, and P. J. Gray Jr., “Cell stress proteins: novel immunotherapeutics,” Novartis Foundation Symposium, vol. 291, pp. 115–131, 2008. View at Google Scholar · View at Scopus
  31. S. Patury, Y. Miyata, and J. E. Gestwicki, “Pharmacological targeting of the Hsp70 chaperone,” Current Topics in Medicinal Chemistry, vol. 9, no. 15, pp. 1337–1351, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Rohde, M. Daugaard, M. H. Jensen, K. Helin, J. Nylandsted, and M. Jaattela, “Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms,” Genes and Development, vol. 19, no. 5, pp. 570–582, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. J. Nylandsted, M. Rohde, K. Brand, L. Bastholm, F. Elling, and M. Jaattela, “Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 14, pp. 7871–7876, 2000. View at Google Scholar · View at Scopus
  34. T. Kirkegaard, A. G. Roth, N. H. Petersen et al., “Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology,” Nature, vol. 463, no. 7280, pp. 549–553, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. R. Z. Orlowski and D. J. Kuhn, “Proteasome inhibitors in cancer therapy: lessons from the first decade,” Clinical Cancer Research, vol. 14, no. 6, pp. 1649–1657, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. C. G. Evans, L. Chang, and J. E. Gestwicki, “Heat shock protein 70 (Hsp70) as an emerging drug target,” Journal of Medicinal Chemistry, vol. 53, no. 12, pp. 4585–4602, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. K. Polzer, L. Joosten, J. Gasser et al., “Interleukin-1 is essential for systemic inflammatory bone loss,” Annals of the Rheumatic Diseases, vol. 69, no. 1, pp. 284–290, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. R. LeBlanc, L. P. Catley, T. Hideshima et al., “Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model,” Cancer Research, vol. 62, no. 17, pp. 4996–5000, 2002. View at Google Scholar · View at Scopus
  39. H. Zhang, V. Vakil, M. Braunstein et al., “Circulating endothelial progenitor cells in multiple myeloma: implications and significance,” Blood, vol. 105, no. 8, pp. 3286–3294, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. M. Braunstein, T. Ozcelik, S. Bagislar et al., “Endothelial progenitor cells display clonal restriction in multiple myeloma,” BMC Cancer, vol. 6, article 161, 2006. View at Publisher · View at Google Scholar · View at PubMed
  41. G. Anderson, M. Gries, N. Kurihara et al., “Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1,” Blood, vol. 107, no. 8, pp. 3098–3105, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. M. Schroder and R. J. Kaufman, “The mammalian unfolded protein response,” Annual Review of Biochemistry, vol. 74, pp. 739–789, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. G. Bianchi, L. Oliva, P. Cascio et al., “The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition,” Blood, vol. 113, no. 13, pp. 3040–3049, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. T. Hideshima, P. Richardson, D. Chauhan et al., “The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells,” Cancer Research, vol. 61, no. 7, pp. 3071–3076, 2001. View at Google Scholar · View at Scopus
  45. S. Bernales, K. L. McDonald, and P. Walter, “Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response,” PLoS Biology, vol. 4, no. 12, Article ID e423, 2006. View at Publisher · View at Google Scholar · View at PubMed
  46. M. Nakamura, T. Gotoh, Y. Okuno et al., “Activation of the endoplasmic reticulum stress pathway is associated with survival of myeloma cells,” Leukemia and Lymphoma, vol. 47, no. 3, pp. 531–539, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. S. Cenci, A. Mezghrani, P. Cascio et al., “Progressively impaired proteasomal capacity during terminal plasma cell differentiation,” EMBO Journal, vol. 25, no. 5, pp. 1104–1113, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. S. S. Vembar and J. L. Brodsky, “One step at a time: endoplasmic reticulum-associated degradation,” Nature Reviews Molecular Cell Biology, vol. 9, no. 12, pp. 944–957, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. A. Buchberger, B. Bukau, and T. Sommer, “Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms,” Molecular Cell, vol. 40, no. 2, pp. 238–252, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. A. F. Gazdar, H. K. Oie, I. R. Kirsch, and G. F. Hollis, “Establishment and characterization of a human plasma cell myeloma culture having a rearranged cellular myc proto-oncogene,” Blood, vol. 67, no. 6, pp. 1542–1549, 1986. View at Google Scholar · View at Scopus
  51. C. Jolly and R. I. Morimoto, “Role of the heat shock response and molecular chaperones in oncogenesis and cell death,” Journal of the National Cancer Institute, vol. 92, no. 19, pp. 1564–1572, 2000. View at Google Scholar · View at Scopus
  52. G. M. Rigolin, C. Fraulini, M. Ciccone et al., “Neoplastic circulating endothelial cells in multiple myeloma with 13q14 deletion,” Blood, vol. 107, no. 6, pp. 2531–2535, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. K. Tanabe, T. Tokumoto, N. Ishikawa et al., “Effect of Deoxyspergualin on the long-term outcome of renal transplantation,” Transplantation Proceedings, vol. 32, no. 7, pp. 1745–1746, 2000. View at Publisher · View at Google Scholar · View at Scopus
  54. K. Nadeau, S. G. Nadler, M. Saulnier, M. A. Tepper, and C. T. Walsh, “Quantitation of the interaction of the immunosuppressant deoxyspergualin and analogs with hsc70 and hsp90,” Biochemistry, vol. 33, no. 9, pp. 2561–2567, 1994. View at Google Scholar · View at Scopus
  55. S. Wisen, E. B. Bertelsen, A. D. Thompson et al., “Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40,” ACS Chemical Biology, vol. 5, no. 6, pp. 611–622, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus