301
Views
30
CrossRef citations to date
0
Altmetric
Original Articles: Research

The oral protein-kinase C β inhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines

, , , , , , , , , , , & show all
Pages 1374-1383 | Received 11 Feb 2008, Accepted 24 Mar 2008, Published online: 01 Jul 2009

References

  • Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel P L, Chesi M, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64: 1546–1558
  • Ferlin M, Noraz N, Hertogh C, Brochier J, Taylor N, Klein B. Insulin-like growth factor induces the survival and proliferation of myeloma cells through an interleukin-6-independent transduction pathway. Br J Haematol 2000; 111: 626–634
  • Freund G G, Kulas D T, Mooney R A. Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226. J Immunol 1993; 151: 1811–1820
  • Klein B, Zhang X G, Lu Z Y, Bataille R. Interleukin-6 in human multiple myeloma. Blood 1995; 85: 863–872
  • Sirohi B, Powles R. Multiple myeloma. Lancet 2004; 363: 875–887
  • Richardson P G, Mitsiades C S, Hideshima T, Anderson K C. Novel biological therapies for the treatment of multiple myeloma. Best Pract Res Clin Haematol 2005; 18: 619–634
  • van de Donk N W, Lokhorst H M, Bloem A C. Growth factors and antiapoptotic signaling pathways in multiple myeloma. Leukemia 2005; 19: 2177–2185
  • Goekjian P G, Jirousek M R. Protein kinase C inhibitors as novel anticancer drugs. Expert Opin Invest Drugs 2001; 10: 2117–2140
  • Shipp M A, Ross K N, Tamayo P, Weng A P, Kutok J L, Aguiar R C, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 2002; 8: 68–74
  • Hans C P, Weisenburger D D, Greiner T C, Chan W C, Aoun P, Cochran G T, et al. Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma. Mod Pathol 2005; 18: 1377–1384
  • Graff J R, McNulty A M, Hanna K R, Konicek B W, Lynch R L, Bailey S N, et al. The protein kinase C beta selective inhibitor, Enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Res 2005; 65: 7462–7469
  • Aeder S E, Martin P M, Soh J W, Hussaini I M. PKC-beta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene 2004; 23: 9062–9069
  • Kawakami Y, Nishimoto H, Kitaura J, Maeda-Yamamoto M, Kato R M, Littman D R, et al. Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion. J Biol Chem 2004; 279: 47720–47725
  • Partovian C, Simons M. Regulation of protein kinase B/Akt activity and Ser473 phosphorylation by protein kinase C alpha in endothelial cells. Cell Signal 2004; 16: 951–957
  • Martelli A M, Nyakern M, Tabellini G, Bortul R, Tazzari P L, Evangelisti C, et al. Phosphoinositide 3-Kinase/AKT signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 2006; 20: 911–928
  • Miranda M B, Johnson D E. Signal transduction pathways that contribute to myeloid differentiation. Leukemia 2007; 21: 1363–1377
  • Nyakern M, Tazzari P L, Finelli C, Bosi C, Follo M Y, Grafone T, et al. Frequent elevation of AKT kinase phosphorilation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients. Leukemia 2006; 20: 230–238
  • Papa V, Tazzari P L, Cappellini A, Cappellini A, Ricci F, Billi A M, et al. Proapoptotic activity and chemosensitizing effect of the novel AKT inhibitor perifosine in acute myelogenous leukemia cells. Leukemia 2008; 22: 147–160
  • Hsu J, Shi Y, Krajewski S, Renner S, Fisher M, Reed J C, et al. The AKT kinase is activated in multiple myeloma tumor cells. Blood 2001; 98: 2853–2855
  • Tu Y, Gardner A, Lichtenstein A. The phosphatidylinositol 3-kinase/AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses. Cancer Res 2000; 60: 6763–6770
  • Pene F, Claessens Y E, Muller O, Viguie F, Mayeux P, Dreyfus F. Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma. Oncogene 2002; 21: 6587–6597
  • Keyes K A, Mann L, Sherman M, Galbreath E, Schirtzinger L, Ballard D. LY317615 decreases plasma VEGF levels in human tumor xenograft-bearing mice. Cancer Chemother Pharmacol 2004; 53: 133–140
  • Teicher B A, Alvarez E, Menon K, Esterman M A, Considine E, Shih C, et al. Antiangiogenic effects of a protein kinase C beta-selective small molecule. Cancer Chemother Pharmacol 2002; 49: 69–77
  • Querfeld C, Rizvi M A, Kuzel T M, Guitart J, Rademaker A, Sabharwal S S, et al. The selective protein kinase C beta inhibitor enzastaurin induces apoptosis in cutaneous T-cell lymphoma cell lines through the AKT pathway. J Invest Dermatol 2006; 126: 1641–1647
  • Rizvi M A, Ghias K, Davies K M, Ma C, Weinberg F, Munshi H G, et al. Enzastaurin (LY317615), a protein kinase C beta inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines. Mol Cancer Ther 2006; 5: 1783–1789
  • Podar K, Raab M S, Zhang J, McMillin D, Breitkreutz I, Tai Y T, et al. Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl). Blood 2007; 109: 1669–1677
  • Baumann P, Armann J, Mandl-Weber S, Grün G, Oduncu F, Schmidmaier R. Inhibitors of protein kinase C sensitise multiple myeloma cells to common genotoxic drugs. Eur J Haematol 2008; 80: 37–45
  • Verdelli D, Mattioli M, Fabris S, Nobili L, Intini D, Guerneri S, et al. Molecular and biological characterization of three novel interleukin-6-dependent human myeloma cell lines. Haematologica 2005; 90: 1541–1548
  • Drexler H G, Matsuo Y. Malignant hematopoietic cell lines: in vitro models for the study of multiple myeloma and plasma cell leukemia. Leuk Res 2000; 24: 681–703
  • Inoue J, Otsuki T, Hirasawa A, Imoto I, Matsuo Y, Shimizu S, et al. Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug resistance phenotype in multiple myeloma. Am J Pathol 2004; 165: 71–81
  • Ronchetti D, Greco A, Compasso S, Colombo G, Dell'Era P, Otsuki T, et al. Deregulated FGFR3 mutants in multiple myeloma cell lines with t(4;14): comparative analysis of Y373C, K650E and the novel G384D mutations. Oncogene 2001; 20: 3553–3562
  • Chou T C, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22: 27–55
  • Chou T C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006; 58: 621–681
  • Moreau A S, Jia X, Ngo H T, Leleu X, O'Sullivan G, Alsayed Y, et al. Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom's Macroglobulinemia. Blood 2007; 109: 4964–4972
  • Carducci M A, Musib L, Kies M S, Pili R, Truong M, Brahmer J R, et al. Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer. J Clin Oncol 2006; 24: 4092–4099

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.