Targeting PKC in multiple myeloma: In vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl)

Blood

Volumn 109, Issue 4, 2007, Pages 1669-1677

  Podar, Klaus ^a,d   Raab, Marc S ^a,b   Zhang, Jing ^a   McMillin, Douglas ^a   Breitkreutz, Iris ^a   Tai, Yu Tzu ^a   Lin, Boris K ^c   Munshi, Nikhil ^a   Hideshima, Teru ^a   Chauhan, Dharminder ^a   Anderson, Kenneth C ^a,d  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c ELI LILLY AND COMPANY   (United States)

^d DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BORTEZOMIB; CYTOKINE; ENZASTAURIN; FIBRONECTIN; GROWTH FACTOR; INTERLEUKIN 6; ISOENZYME; LENALIDOMIDE; MARCKS PROTEIN; MELPHALAN; PHORBOL ESTER; PROTEIN KINASE C; PROTEIN KINASE C MU; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MARROW; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENTIATION; DRUG SCREENING; DRUG TARGETING; ENDOTHELIUM CELL; ENZYME ACTIVATION; ENZYME INACTIVATION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; IC 50; IMMUNOHISTOCHEMISTRY; MOUSE; MULTIPLE MYELOMA; NONHUMAN; PRIORITY JOURNAL; STROMA CELL; TREATMENT OUTCOME; TUMOR GROWTH;

EID: 33846914141     PISSN: 00064971     EISSN: 00064971     Source Type: Journal    
DOI: 10.1182/blood-2006-08-042747     Document Type: Article

References (47)

1. Nishizuka Y. The Albert Lasker Medical Awards. The family of protein kinase C for signal transduction. JAMA. 1989;262:1826-1833.
2. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986;233:305-312.
3. Asaoka Y, Nakamura S, Yoshida K, Nishizuka Y. Protein kinase C, calcium and phospholipid degradation. Trends Biochem Sci. 1992;17:414-417.
4. Dekker LV, Parker PJ. Protein kinase C - a question of specificity. Trends Biochem Sci. 1994;19:73-77.
5. Nishizuka Y. Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 1995;9:484-496.
6. Newton AC. Protein kinase C: structure, function, and regulation. J Biol Chem. 1995;270:28495-28498.
7. Newton AC. Regulation of protein kinase C. Curr Opin Cell Biol. 1997;9:161-167.
8. Berenblum I. The mechanism of carcinogenesis: a study of the significance of carcinogenic action and related phenomena. Cancer Res. 1941;1:807-814.
9. Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982;257:7847-7851.
10. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984;308:693-698.
11. Nishizuka Y. Discovery and prospect of protein kinase C research: epilogue. J Biochem (Tokyo). 2003;133:155-158.
12. O'Brian C, Vogel VG, Singletary SE, Ward NE. Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue. Cancer Res. 1989;49:3215-3217.
13. Takenaga K, Takahashi K. Effects of 12-O-tetradecanoylphorbol-13-acetate on adhesiveness and lung-colonizing ability of Lewis lung carcinoma cells. Cancer Res. 1986;46:375-380.
14. Schwartz GK, Jiang J, Kelsen D, Albino AP. Protein kinase C: a novel target for inhibiting gastric cancer cell invasion. J Natl Cancer Inst. 1993;85:402-407.
15. Gokmen-Polar Y, Murray NR, Velasco MA, Gatalica Z, Fields AP. Elevated protein kinase C betaII is an early promotive event in colon carcinogenesis. Cancer Res. 2001;61:1375-1381.
16. da Rocha AB, Mans DR, Regner A, Schwartsmann G. Targeting protein kinase C: new therapeutic opportunities against high-grade malignant gliomas? Oncologist. 2002;7:17-33.
17. Dean N, McKay R, Miraglia L, et al. Inhibition of growth of human tumor cell lines in nude mice by an antisense of oligonucleotide inhibitor of protein kinase C-alpha expression. Cancer Res. 1996;56:3499-3507.
18. Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002;8:68-74.
19. Hans CP, Weisenburger DD, Greiner TC, 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.
20. Felli MP, Vacca A, Calce A, et al. PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia. Oncogene. 2005;24:992-1000.
21. Gorelik G, Barreiro Arcos ML, Klecha AJ, Cremaschi GA. Differential expression of protein kinase C isoenzymes related to high nitric oxide synthase activity in a T lymphoma cell line. Biochim Biophys Acta. 2002;1588:179-188.
22. Villalba M, Kasibhatla S, Genestier L, Mahboubi A, Green DR, Altman A. Protein kinase ctheta cooperates with calcineurin to induce Fas ligand expression during activation-induced T cell death. J Immunol. 1999;163:5813-5819.
23. Goekjian PG, Jirousek MR. Protein kinase C inhibitors as novel anticancer drugs. Expert Opin Investig Drugs. 2001;10:2117-2140.
24. Taylor CJ, Motamed K, Lilly B. Protein kinase C and downstream signaling pathways in a three-dimensional model of phorbol ester-induced angiogenesis. Angiogenesis. 2006;9:39-51.
25. Graff JR, McNulty AM, Hanna KR, et al. The protein kinase Cbeta-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.
26. Keyes KA, Mann L, Sherman M, et al. LY317615 decreases plasma VEGF levels in human tumor xenograft-bearing mice. Cancer Chemother Pharmacol. 2004;53:133-140.
27. Green LJ, Marder P, Ray C, et al. Development and validation of a drug activity biomarker that shows target inhibition in cancer patients receiving enzastaurin, a novel protein kinase C-beta inhibitor. Clin Cancer Res. 2006;12:3408-3415.
28. Herbst RS, Thornton DE, Kies MS. Phase 1 study of LY317615, a protein kinase C beta inhibitor. Proc ASCO. 2002;21:82a.
29. Parant MR, Klein B, Vial H. Abnormal behavior of protein kinase C in the human myeloma cell line, RPMI 8226. FEBS Lett. 1990;269:331-335.
30. Ni H, Ergin M, Tibudan SS, Denning MF, Izban KF, Alkan S. Protein kinase C-delta is commonly expressed in multiple myeloma cells and its downregulation by rottlerin causes apoptosis. Br J Haematol. 2003;121:849-856.
31. Thabard W, Collette M, Bataille R, Amiot M. Protein kinase C delta and eta isoenzymes control the shedding of the interleukin 6 receptor alpha in myeloma cells. Biochem J. 2001;358:193-200.
32. Podar K, Tai YT, Lin BK, et al. Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta 1 integrin-and phosphatidylinositol 3-kinase-dependent PKC alpha activation. J Biol Chem. 2002;277:7875-7881.
33. Qiang YW, Walsh K, Yao L, et al. Wnts induce migration and invasion of myeloma plasma cells. Blood. 2005;106:1786-1793.
34. Chauhan D, Pandey P, Ogata A, et al. Cytochrome c-dependent and -independent induction of apoptosis in multiple myeloma cells. J Biol Chem. 1997;272:29995-29997.
35. Podar K, Anderson KC. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood. 2005;105:1383-1395.
36. Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J Jr. Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma. Blood. 2005;106:296-303.
37. Dring AM, Davies FE, Fenton JA, et al. A global expression-based analysis of the consequences of the t(4;14) translocation in myeloma. Clin Cancer Res. 2004;10:5692-5701.
38. Podar K, Shringarpure R, Tai YT, et al. Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. Cancer Res. 2004;64:7500-7506.
39. Chauhan D, Catley L, Hideshima T, et al. 2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells. Blood. 2002;100:2187-2194.
40. Rizvi MA, Ghias K, Davies KM, et al. Enzastaurin (LY317615), a protein kinase Cbeta inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines. Mol Cancer Ther. 2006;5:1783-1789.
41. Kaufman JL, Lonial S. Proteasome inhibition: novel therapy for multiple myeloma. Onkologie. 2006;29:162-168.
42. Kumar S, Rajkumar SV. Thalidomide and lenalidomide in the treatment of multiple myeloma. Eur J Cancer. 2006;42:1612-1622.
43. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860-1873.
44. Montesano R, Orci L. Tumor-promoting phorbol esters induce angiogenesis in vitro. Cell. 1985;42:469-477.
45. Teicher BA, Alvarez E, Menon K, et al. Antiangiogenic effects of a protein kinase Cbeta-selective small molecule. Cancer Chemother Pharmacol. 2002;49:69-77.
46. Martelli AM, Evangelisti C, Nyakern M, Manzoli FA. Nuclear protein kinase C. Biochim Biophys Acta. 2006;1761:542-551.
47. Chen J, Lee BH, Williams IR, et al. FGFR3 as a therapeutic target of the small molecule inhibitor PKC412 in hematopoietic malignancies. Oncogene. 2005;24:8259-8267.