The peptide-semicarbazone S-2209, a representative of a new class of proteasome inhibitors, induces apoptosis and cell growth arrest in multiple myeloma cells

British Journal of Haematology

Volumn 144, Issue 6, 2009, Pages 875-886

  Baumann, Philipp ^a   Müller, Karin ^a   Mandl Weber, Sonja ^a   Leban, Johann ^b   Doblhofer, Robert ^b   Ammendola, Astrid ^b   Baumgartner, Roland ^b   Oduncu, Fuat ^a   Schmidmaier, Ralf ^a  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b 4SC AG   (Germany)

Author keywords

Multiple myeloma; NF B; P53; Proteasome inhibitor; S 2209

Indexed keywords

1 [1 [1 [(2,4 DIOXO IMIDAZOLIDIN 1 YLIMINO)METHYL] 2 PHENYLETHYLCARBAMOYL] 2 (1H INDOL 3 YL)ETHYLCARBAMOYL] 2 (1H INDOL); BORTEZOMIB; CREATININE; DOXORUBICIN; HEMOGLOBIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIVER ENZYME; MELPHALAN; PROTEASOME INHIBITOR; PROTEIN MCL 1; PROTEIN P53; S 2209; STRESS ACTIVATED PROTEIN KINASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL GROWTH; CELL PROLIFERATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG POTENTIATION; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; MALE; MAXIMUM TOLERATED DOSE; MULTIPLE MYELOMA; MYELOMA CELL; NONHUMAN; PRIORITY JOURNAL; RAT;

ANIMALS; ANTIMETABOLITES; APOPTOSIS; CELL DEATH; CELL LINE, TUMOR; DOXORUBICIN; DRUG SYNERGISM; HUMANS; MALE; MAP KINASE KINASE 4; MAXIMUM TOLERATED DOSE; MELPHALAN; MULTIPLE MYELOMA; NF-KAPPA B; PEPTIDES; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTO-ONCOGENE PROTEINS C-BCL-2; RATS; RATS, WISTAR; SEMICARBAZONES; TOXICITY TESTS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 60749132544     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/j.1365-2141.2008.07570.x     Document Type: Article

References (45)

1. Adams, J. (2002) Preclinical and clinical evaluation of proteasome inhibitor PS-341 for the treatment of cancer. Current Opinion in Chemical Biology, 6, 493 500.
2. Alkalay, I., Yaron, A., Hatzubai, A., Orian, A., Ciechanover, A. Ben-Neriah, Y. (1995) Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences of the United States of America, 92, 10599 10603.
3. Attal, M., Harousseau, J.L., Stoppa, A.M., Sotto, J.J., Fuzibet, J.G., Rossi, J.F., Casassus, P., Maisonneuve, H., Facon, T., Ifrah, N., Payen, C. Bataille, R. (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. New England Journal of Medicine, 335, 91 97.
4. Attal, M., Harousseau, J.L., Facon, T., Guilhot, F., Doyen, C., Fuzibet, J.G., Monconduit, M., Hulin, C., Caillot, D., Bouabdallah, R., Voillat, L. Sotto, J.J. (2003) Single versus double autologous stem-cell transplantation for multiple myeloma. New England Journal of Medicine, 349, 2495 2502.
5. Bae, I., Fan, S., Bhatia, K., Kohn, K.W., Fornace, Jr., A.J. O'Connor, P.M. (1995) Relationships between G1 arrest and stability of the p53 and p21Cip1/Waf1 proteins following gamma-irradiation of human lymphoma cells. Cancer Research, 55, 2387 2393.
6. Barlogie, B., Jagannath, S., Desikan, K.R., Mattox, S., Vesole, D., Siegel, D., Tricot, G., Munshi, N., Fassas, A., Singhal, S., Mehta, J., Anaissie, E., Dhodapkar, D., Naucke, S., Cromer, J., Sawyer, J., Epstein, J., Spoon, D., Ayers, D., Cheson, B. Crowley, J. (1999) Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood, 93, 55 65.
7. Baumann, P., Mandl-Weber, S., Emmerich, B., Straka, C. Schmidmaier, R. (2007) Activation of adenosine monophosphate activated protein kinase inhibits growth of multiple myeloma cells. Experimental Cell Research, 313, 3592 3603.
8. Baumann, P., Mandl-Weber, S., Oduncu, F. Schmidmaier, R. (2008) Alkylating agents induce activation of NFkappaB in multiple myeloma cells. Leukemia Research, 32, 1144 1147.
9. Chauhan, D., Li, G., Hideshima, T., Podar, K., Mitsiades, C., Mitsiades, N., Munshi, N., Kharbanda, S. Anderson, K.C. (2003) JNK-dependent release of mitochondrial protein, Smac, during apoptosis in multiple myeloma (MM) cells. Journal of Biological Chemistry, 278, 17593 17596.
10. Child, J.A., Morgan, G.J., Davies, F.E., Owen, R.G., Bell, S.E., Hawkins, K., Brown, J., Drayson, M.T., Selby, P.J. Medical Research Council Adult Leukaemia Working Party (2003) High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. New England Journal of Medicine, 348, 1875 1883.
11. Dalton, W.S. (2004) The proteasome. Seminars in Oncology, 31, 3 9.
12. Dalton, W.S., Hazlehurst, L., Shain, K., Landowski, T. Alsina, M. (2004) Targeting the bone marrow microenvironment in hematologic malignancies. Seminars in Hematology, 41, 1 5.
13. Davenport, E.L., Moore, H.E., Dunlop, A.S., Sharp, S.Y., Workman, P., Morgan, G.J. Davies, F.E. (2007) Heat shock protein inhibition is associated with activation of the unfolded protein response pathway in myeloma plasma cells. Blood, 110, 2641 2649.
14. Glasmacher, A., Hahn, C., Hoffmann, F., Naumann, R., Goldschmidt, H., von Lilienfeld-Toal, M., Orlopp, K., Schmidt-Wolf, I. Gorschluter, M. (2006) A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. British Journal Haematology, 132, 584 593.
15. Gregory, W.M., Richards, M.A. Malpas, J.S. (1992) Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. Journal of Clinical Oncology, 10, 334 342.
16. Haas, M., Page, S., Page, M., Neumann, F.J., Marx, N., Adam, M., Ziegler-Heitbrock, H.W., Neumeier, D. Brand, K. (1998) Effect of proteasome inhibitors on monocytic IkappaB-alpha and -beta depletion, NF-kappaB activation, and cytokine production. Journal of Leukocyte Biology, 63, 395 404.
17. Hideshima, T. Anderson, K.C. (2002) Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nature Reviews. Cancer, 2, 927 937.
18. Hideshima, T., Richardson, P., Chauhan, D., Palombella, V.J., Elliott, P.J., Adams, J. Anderson, K.C. (2001) The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Research, 61, 3071 3076.
19. Hideshima, T., Catley, L., Yasui, H., Ishitsuka, K., Raje, N., Mitsiades, C., Podar, K., Munshi, N.C., Chauhan, D., Richardson, P.G. Anderson, K.C. (2006) Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood, 107, 4053 4062.
20. Hideshima, T., Catley, L., Raje, N., Chauhan, D., Podar, K., Mitsiades, C., Tai, Y.T., Vallet, S., Kiziltepe, T., Ocio, E., Ikeda, H., Okawa, Y., Hideshima, H., Munshi, N.C., Yasui, H., Richardson, P.G. Anderson, K.C. (2007) Inhibition of Akt induces significant downregulation of survivin and cytotoxicity in human multiple myeloma cells. British Journal Haematology, 138, 783 791.
21. Kanagasabaphy, P., Morgan, G.J. Davies, F.E. (2007) Proteasome inhibition and multiple myeloma. Current Opinion in Investigational Drugs, 8, 447 451.
22. Kisselev, A.F. Goldberg, A.L. (2001) Proteasome inhibitors: from research tools to drug candidates. Chemistry & Biology, 8, 739 758.
23. Leban, J., Blisse, M., Krauss, B., Rath, S., Baumgartner, R. Seifert, M.H. (2008) Proteasome inhibition by peptide-semicarbazones. Bioorganic & Medicinal Chemistry, 16, 4579 4588.
24. Loda, M., Cukor, B., Tam, S.W., Lavin, P., Fiorentino, M., Draetta, G.F., Jessup, J.M. Pagano, M. (1997) Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nature Medicine, 3, 231 234.
25. Ma, M.H., Yang, H.H., Parker, K., Manyak, S., Friedman, J.M., Altamirano, C., Wu, Z.Q., Borad, M.J., Frantzen, M., Roussos, E., Neeser, J., Mikail, A., Adams, J., Sjak-Shie, N., Vescio, R.A. Berenson, J.R. (2003) The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. Clinical Cancer Research, 9, 1136 1144.
26. Mateos, M.V., Hernández, J.M., Hernández, M.T., Gutiérrez, N.C., Palomera, L., Fuertes, M., Díaz-Mediavilla, J., Lahuerta, J.J., de la Rubia, J., Terol, M.J., Sureda, A., Bargay, J., Ribas, P., de Arriba, F., Alegre, A., Oriol, A., Carrera, D., García-Laraña, J., García-Sanz, R., Bladé, J., Prósper, F., Mateo, G., Esseltine, D.L., van de Velde, H. San Miguel, J.F. (2006) Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood, 108, 2165 2172.
27. Myeloma Trialists' Collaborative Group (1998) Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Journal of Clinical Oncology, 16, 3832 3842.
28. Nakanishi, C. Toi, M. (2005) Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nature Reviews. Cancer, 5, 297 309.
29. Navas, T.A., Nguyen, A.N., Hideshima, T., Reddy, M., Ma, J.Y., Haghnazari, E., Henson, M., Stebbins, E.G., Kerr, I., O'Young, G., Kapoun, A.M., Chakravarty, S., Mavunkel, B., Perumattam, J., Luedtke, G., Dugar, S., Medicherla, S., Protter, A.A., Schreiner, G.F., Anderson, K.C. Higgins, L.S. (2006) Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo. Leukemia, 20, 1017 1027.
30. Orlowski, R.Z. Kuhn, D.J. (2008) Proteasome inhibitors in cancer therapy: lessons from the first decade. Clinical Cancer Research, 14, 1649 1657.
31. Palumbo, A., Bringhen, S., Petrucci, M.T., Musto, P., Rossini, F., Nunzi, M., Lauta, V.M., Bergonzi, C., Barbui, A., Caravita, T., Capaldi, A., Pregno, P., Guglielmelli, T., Grasso, M., Callea, V., Bertola, A., Cavallo, F., Falco, P., Rus, C., Massaia, M., Mandelli, F., Carella, A.M., Pogliani, E., Liberati, A.M., Dammacco, F., Ciccone, G. Boccadoro, M. (2004) Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood, 104, 3052 3057.
32. Palumbo, A., Ambrosini, M.T., Benevolo, G., Pregno, P., Pescosta, N., Callea, V., Cangialosi, C., Caravita, T., Morabito, F., Musto, P., Bringhen, S., Falco, P., Avonto, I., Cavallo, F., Boccadoro, M. Italian Multiple Myeloma Network; Gruppo Italiano Malattie Ematologicche dell'Adulto (2007) Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood, 109, 2767 2772.
33. Palumbo, A., Miguel, J.S., Sonneveld, P., Moreau, P., Drach, J., Morgan, G. Einsele, H. (2008a) Lenalidomide: a new therapy for multiple myeloma. Cancer Treatment Reviews, 34, 283 291.
34. Palumbo, A., Gay, F., Bringhen, S., Falcone, A., Pescosta, N., Callea, V., Caravita, T., Morabito, F., Magarotto, V., Ruggeri, M., Avonto, I., Musto, P., Cascavilla, N., Bruno, B. Boccadoro, M. (2008b) Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma. Annals of Oncology, 19, 1160 1165.
35. Pei, X.Y., Dai, Y. Grant, S. (2003) The proteasome inhibitor bortezomib promotes mitochondrial injury and apoptosis induced by the small molecule Bcl-2 inhibitor HA14-1 in multiple myeloma cells. Leukemia, 17, 2036 2045.
36. Piva, R., Belardo, G. Santoro, M.G. (2006) NF-kappaB: a stress-regulated switch for cell survival. Antioxidants Redox Signaling, 8, 478 486.
37. Richardson, P.G., Sonneveld, P., Schuster, M.W., Irwin, D., Stadtmauer, E.A., Facon, T., Harousseau, J.L., Ben-Yehuda, D., Lonial, S., Goldschmidt, H., Reece, D., San-Miguel, J.F., Bladé, J., Boccadoro, M., Cavenagh, J., Dalton, W.S., Boral, A.L., Esseltine, D.L., Porter, J.B., Schenkein, D., Anderson, K.C. Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. New England Journal of Medicine, 352, 2487 2498.
38. Scheffner, M., Huibregtse, J.M., Vierstra, R.D. Howley, P.M. (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell, 75, 495 505.
39. Scherer, D.C., Brockman, J.A., Chen, Z., Maniatis, T. Ballard, D.W. (1995) Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Proceedings of the National Academy of Sciences of the United States of America, 92, 11259 11263.
40. Schmidmaier, R., Baumann, P., Simsek, M., Dayyani, F., Emmerich, B. Meinhardt, G. (2004) The HMG-CoA reductase inhibitor simvastatin overcomes cell adhesion-mediated drug resistance in multiple myeloma by geranylgeranylation of Rho protein and activation of Rho kinase. Blood, 104, 1825 1832.
41. Singhal, S., Mehta, J., Desikan, R., Ayers, D., Roberson, P., Eddlemon, P., Munshi, N., Anaissie, E., Wilson, C., Dhodapkar, M., Zeddis, J. Barlogie, B. (1999) Antitumor activity of thalidomide in refractory multiple myeloma. New England Journal of Medicine, 341, 1565 1571.
42. Spencer, E., Jiang, J. Chen, Z.J. (1999) Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP. Genes and Development, 13, 284 294.
43. Thomas, S.K., Richards, T.A. Weber, D.M. (2007) Lenalidomide in multiple myeloma. Best Practice & Research. Clinical Haematology, 20, 717 735.
44. Tournier, C., Hess, P., Yang, D.D., Xu, J., Turner, T.K., Nimnual, A., Bar-Sagi, D., Jones, S.N., Flavell, R.A. Davis, R.J. (2000) Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science, 288, 870 874.
45. Zavrski, I., Jakob, C., Kaiser, M., Fleissner, C., Heider, U. Sezer, O. (2007) Molecular and clinical aspects of proteasome inhibition in the treatment of cancer. Recent Results in Cancer Research, 176, 165 176.