Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity with dexamethasone

Journal of Molecular Medicine

Volumn 90, Issue 6, 2012, Pages 695-706

  Zheng, Yuhuan ^a   Yang, Jing ^a   Qian, Jianfei ^a   Zhang, Liang ^a   Lu, Yong ^a   Li, Haiyan ^a   Lin, Heather ^a   Lan, Yongsheng ^a   Liu, Zhiqiang ^a   He, Jin ^a   Hong, Sungyoul ^a   Thomas, Sheeba ^a   Shah, Jatin ^a   Baladandayuthapani, Veera ^a   Kwak, Larry W ^a   Yi, Qing ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Apoptosis; BKM120; Chemotherapy; Multiple myeloma; PI3K

Indexed keywords

BIM PROTEIN; BUPARLISIB; DEXAMETHASONE; INTERLEUKIN 6; PROTEIN P27; SOMATOMEDIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BONE MARROW CELL; CANCER GROWTH; CANCER SURVIVAL; CELL CYCLE ARREST; CELL GROWTH; CONTROLLED STUDY; CYTOTOXICITY; DOWN REGULATION; DRUG EFFICACY; FEMALE; HUMAN; HUMAN CELL; IN VIVO STUDY; LYMPHOCYTE; MOUSE; MYELOMA; MYELOMA CELL; NONHUMAN; PROTEIN EXPRESSION;

AMINOPYRIDINES; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; DEXAMETHASONE; DRUG SYNERGISM; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; MICE; MICE, SCID; MORPHOLINES; MULTIPLE MYELOMA;

EID: 84862701242     PISSN: 09462716     EISSN: 14321440     Source Type: Journal    
DOI: 10.1007/s00109-011-0849-9     Document Type: Article

References (35)

1. RA Kyle SV Rajkumar 2004 Multiple myeloma N Engl J Med 351 1860 1873 15509819 10.1056/NEJMra041875 1:CAS:528:DC%2BD2cXptFChtLk%3D
2. Jagannath S, Kyle RA, Palumbo A, Siegel DS, Cunningham S, Berenson J (2010) The current status and future of multiple myeloma in the clinic. Clin Lymphoma Myeloma Leuk 10: 28-43
3. A Jemal R Siegel E Ward Y Hao J Xu MJ Thun 2009 Cancer statistics, 2009 CA Cancer J Clin 59 225 249 19474385 10.3322/caac.20006
4. G Di Paolo P De Camilli 2006 Phosphoinositides in cell regulation and membrane dynamics Nature 443 651 657 17035995 10.1038/nature05185
5. JA Engelman J Luo LC Cantley 2006 The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism Nat Rev Genet 7 606 619 16847462 10.1038/nrg1879 1:CAS:528:DC%2BD28XmvFCnu7Y%3D
6. JA Engelman 2009 Targeting PI3K signalling in cancer: opportunities, challenges and limitations Nat Rev Cancer 9 550 562 19629070 10.1038/nrc2664 1:CAS:528:DC%2BD1MXovFylsrg%3D
7. H Younes X Leleu E Hatjiharissi AS Moreau T Hideshima P Richardson KC Anderson IM Ghobrial 2007 Targeting the phosphatidylinositol 3-kinase pathway in multiple myeloma Clin Cancer Res 13 3771 3775 17606706 10.1158/1078-0432.CCR- 06-2921 1:CAS:528:DC%2BD2sXntFymsb8%3D
8. T Hideshima N Nakamura D Chauhan KC Anderson 2001 Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma Oncogene 20 5991 6000 11593406 10.1038/sj.onc.1204833 1:CAS:528:DC%2BD3MXnsVCjsLw%3D
9. G Descamps C Pellat-Deceunynck Y Szpak R Bataille N Robillard M Amiot 2004 The magnitude of Akt/phosphatidylinositol 3'-kinase proliferating signaling is related to CD45 expression in human myeloma cells J Immunol 173 4953 4959 15470037 1:CAS:528:DC%2BD2cXotFCqtbY%3D
10. RD Harvey S Lonial 2007 PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma Future Oncol 3 639 647 18041916 10.2217/14796694.3.6.639 1:CAS:528:DC%2BD2sXhtlKltLzO
11. Salphati L, Pang J, Plise EG, Chou B, Halladay JS, Olivero AG, Rudewicz PJ, Tian Q, Wong S, Zhang X (2011) Preclinical pharmacokinetics of the novel PI3K inhibitor GDC-0941 and prediction of its pharmacokinetics and efficacy in human. Xenobiotica 41:1088-1099
12. Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, et al. (2011) CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 117:591-594
13. Y Zheng Z Cai S Wang X Zhang J Qian S Hong H Li M Wang J Yang Q Yi 2009 Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis Blood 114 3625 3628 19710503 10.1182/blood-2009-05-220285 1:CAS:528:DC%2BD1MXhtlyjsrrE
14. L Zhao MG Wientjes JL Au 2004 Evaluation of combination chemotherapy: integration of nonlinear regression, curve shift, isobologram, and combination index analyses Clin Cancer Res 10 7994 8004 15585635 10.1158/1078-0432.CCR-04- 1087 1:CAS:528:DC%2BD2cXhtVCrs7rJ
15. JJ Lee M Kong GD Ayers R Lotan 2007 Interaction index and different methods for determining drug interaction in combination therapy J Biopharm Stat 17 461 480 17479394 10.1080/10543400701199593 1:CAS:528:DC%2BD2sXkvVOnsbg%3D
16. YT Tai M Dillon W Song M Leiba XF Li P Burger AI Lee K Podar T Hideshima AG Rice, et al. 2008 Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu Blood 112 1329 1337 17906076 10.1182/blood-2007-08-107292 1:CAS:528:DC%2BD1cXpvVOktL0%3D
17. K Gado G Domjan H Hegyesi A Falus 2000 Role of interleukin-6 in the pathogenesis of multiple myeloma Cell Biol Int 24 195 209 10816321 10.1006/cbir.2000.0497 1:CAS:528:DC%2BD3cXjt1ansr8%3D
18. MA Frassanito A Cusmai G Iodice F Dammacco 2001 Autocrine interleukin-6 production and highly malignant multiple myeloma: relation with resistance to drug-induced apoptosis Blood 97 483 489 11154226 10.1182/blood.V97.2.483 1:CAS:528:DC%2BD3MXlvF2itA%3D%3D
19. Y Shi H Yan P Frost J Gera A Lichtenstein 2005 Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade Mol Cancer Ther 4 1533 1540 16227402 10.1158/1535-7163.MCT-05-0068 1:CAS:528:DC%2BD2MXhtFWhtLjE
20. CS Mitsiades DW McMillin S Klippel T Hideshima D Chauhan PG Richardson NC Munshi KC Anderson 2007 The role of the bone marrow microenvironment in the pathophysiology of myeloma and its significance in the development of more effective therapies Hematol Oncol Clin North Am 21 1007 1034 17996586 10.1016/j.hoc.2007.08.007 vii-viii
21. L O'Connor A Strasser LA O'Reilly G Hausmann JM Adams S Cory DC Huang 1998 Bim: a novel member of the Bcl-2 family that promotes apoptosis EMBO J 17 384 395 9430630 10.1093/emboj/17.2.384
22. A Weber SA Paschen K Heger F Wilfling T Frankenberg H Bauerschmitt BM Seiffert S Kirschnek H Wagner G Hacker 2007 BimS-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins J Cell Biol 177 625 636 17517961 10.1083/jcb.200610148 1:CAS:528:DC%2BD2sXls1ygsr0%3D
23. PF Dijkers RH Medema JW Lammers L Koenderman PJ Coffer 2000 Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1 Curr Biol 10 1201 1204 11050388 10.1016/S0960-9822(00)00728-4 1:CAS:528:DC%2BD3cXotVSrtLs%3D
24. QL Deveraux N Roy HR Stennicke T Van Arsdale Q Zhou SM Srinivasula ES Alnemri GS Salvesen JC Reed 1998 IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases EMBO J 17 2215 2223 9545235 10.1093/emboj/17.8.2215 1:CAS:528:DyaK1cXivFOmsb8%3D
25. AJ Minn CS Kettlun H Liang A Kelekar MG Vander Heiden BS Chang SW Fesik M Fill CB Thompson 1999 Bcl-xL regulates apoptosis by heterodimerization- dependent and -independent mechanisms EMBO J 18 632 643 9927423 10.1093/emboj/18.3.632 1:CAS:528:DyaK1MXhslais7o%3D
26. J Yang J Qian M Wezeman S Wang P Lin M Wang S Yaccoby LW Kwak B Barlogie Q Yi 2006 Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies Cancer Cell 10 295 307 17045207 10.1016/j.ccr.2006.08.025 1:CAS:528:DC%2BD28XhtFCgsbjP
27. WS Dalton 2002 Drug resistance and drug development in multiple myeloma Semin Oncol 29 21 25 12520481 1:CAS:528:DC%2BD3sXlsFOgtw%3D%3D
28. E Kastritis A Palumbo MA Dimopoulos 2009 Treatment of relapsed/refractory multiple myeloma Semin Hematol 46 143 157 19389498 10.1053/j.seminhematol.2009. 01.004 1:CAS:528:DC%2BD1MXmt1WhtL8%3D
29. Ludwig H, Beksac M, Blade J, Boccadoro M, Cavenagh J, Cavo M, Dimopoulos M, Drach J, Einsele H, Facon T, et al. (2010) Current multiple myeloma treatment strategies with novel agents: a European perspective. Oncologist 15:6-25
30. SK Kumar SV Rajkumar A Dispenzieri MQ Lacy SR Hayman FK Buadi SR Zeldenrust D Dingli SJ Russell JA Lust, et al. 2008 Improved survival in multiple myeloma and the impact of novel therapies Blood 111 2516 2520 17975015 10.1182/blood-2007-10-116129 1:CAS:528:DC%2BD1cXivFaktrk%3D
31. F Pene YE Claessens O Muller F Viguie P Mayeux F Dreyfus C Lacombe D Bouscary 2002 Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma Oncogene 21 6587 6597 12242656 10.1038/sj.onc.1205923 1:CAS:528:DC%2BD38XntFemsrw%3D
32. CS Mitsiades NS Mitsiades CJ McMullan V Poulaki R Shringarpure M Akiyama T Hideshima D Chauhan M Joseph TA Libermann, et al. 2004 Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors Cancer Cell 5 221 230 15050914 10.1016/S1535-6108(04)00050-9 1:CAS:528:DC%2BD2cXjtVartbg%3D
33. KE O'Reilly F Rojo QB She D Solit GB Mills D Smith H Lane F Hofmann DJ Hicklin DL Ludwig, et al. 2006 mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt Cancer Res 66 1500 1508 16452206 10.1158/0008-5472.CAN-05-2925
34. DW McMillin M Ooi J Delmore J Negri P Hayden N Mitsiades J Jakubikova SM Maira C Garcia-Echeverria R Schlossman, et al. 2009 Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 Cancer Res 69 5835 5842 19584292 10.1158/0008-5472.CAN-08-4285 1:CAS:528:DC%2BD1MXosV2msbw%3D
35. D Cirstea T Hideshima S Rodig L Santo S Pozzi S Vallet H Ikeda G Perrone G Gorgun K Patel, et al. 2010 Dual inhibition of akt/mammalian target of rapamycin pathway by nanoparticle albumin-bound-rapamycin and perifosine induces antitumor activity in multiple myeloma Mol Cancer Ther 9 963 975 20371718 10.1158/1535-7163.MCT-09-0763 1:CAS:528:DC%2BC3cXktlCqtL4%3D