The small-molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and Jun NH2-terminal kinase-dependent mechanism

Molecular Cancer Therapeutics

Volumn 3, Issue 12, 2004, Pages 1513-1524

  Pei, Xin Yan ^a   Dai, Yun ^a   Grant, Steven ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 6 BROMO 4 (1 CYANO 2 ETHOXY 2 OXOETHYL) 4H CHROMENE 3 CARBOXYLIC ACID ETHYL ESTER; ACETYLCYSTEINE; ANTIOXIDANT; CASPASE; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR; CYTOCHROME C; CYTOTOXIC AGENT; DEXAMETHASONE; FLAVOPIRIDOL; FREE RADICAL; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE P38; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN BID; PROTEIN INHIBITOR; PROTEIN MCL 1; REACTIVE OXYGEN METABOLITE; SECOND MITOCHONDRIAL ACTIVATOR OF CASPASE; SOMATOMEDIN C; STRESS ACTIVATED PROTEIN KINASE;

APOPTOSIS; ARTICLE; BIOSYNTHESIS; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CANCER RESISTANCE; CELL DAMAGE; CELL MEMBRANE POTENTIAL; CELL SURVIVAL; CLONOGENESIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EXPOSURE; DRUG POTENTIATION; ENZYME ACTIVATION; HUMAN; HUMAN CELL; LETHALITY; MITOCHONDRIAL MEMBRANE; MITOCHONDRION; MOLECULAR INTERACTION; MOLECULAR SIZE; MONOTHERAPY; MULTIPLE MYELOMA; MYELOMA CELL; OXIDATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN LOCALIZATION; PROTEIN SECRETION; PROTEIN TRANSPORT;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-X PROTEIN; BENZOPYRANS; BH3 INTERACTING DOMAIN DEATH AGONIST PROTEIN; CARRIER PROTEINS; CYCLIN D1; CYCLIN-DEPENDENT KINASES; CYTOCHROMES C; DRUG SYNERGISM; ENZYME ACTIVATION; ENZYME INHIBITORS; FLAVONOIDS; FREE RADICALS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MEMBRANE POTENTIALS; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MULTIPLE MYELOMA; NEOPLASM PROTEINS; NITRILES; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PIPERIDINES; PROTEIN TRANSPORT; PROTO-ONCOGENE PROTEINS C-BCL-2; TUMOR CELLS, CULTURED;

EID: 12344252927     PISSN: 15357163     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (63)

1. British Committee for Standards in Haematology. Diagnosis and management of multiple myeloma: UK myeloma forum. Br J Haematol 2001;115:522-40.
2. Lauta VM. A review of the cytokine network in multiple myeloma: diagnostic, prognostic, and therapeutic implications. Cancer 2003;97:2440-52.
3. Mileshkin L, Biagi JJ, Mitchell P, et al. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood 2003;102:69-77.
4. Zangari M, Anaissie E, Stopeck A, et al. Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma. Clin Cancer Res 2004;10:88-95.
5. Mitsiades N, Mitsiades CS, Richardson PG, et al. Molecular sequelae of histone deacetylase inhibition in human malignant B cells. Blood 2003;101:4055-62.
6. Orlowski RZ, Stinchcombe TE, Mitchell BS, et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol 2002;20:4420-7.
7. Dai Y, Grant S. Small molecule inhibitors targeting cyclin-dependent kinases as anticancer agents. Curr Oncol Rep 2004;6:123-30.
8. Jiang J, Matranga CB, Cai D, et al. Flavopiridol-induced apoptosis during S phase requires E2F-1 and inhibition of cyclin A-dependent kinase activity. Cancer Res 2003;63:7410-22.
9. Colevas D, Blaylock B, Gravell A. Clinical trials referral resource. Flavopiridol. Oncology (Huntingt) 2002;16:1204-5, 1210-2, 1214.
10. Parker BW, Kaur G, Nieves-Neira W, et al. Early induction of apoptosis in hematopoietic cell lines after exposure to flavopiridol. Blood 1998;91: 458-65.
11. Achenbach TV, Muller R, Slater EP. Bcl-2 independence of flavopiridol-induced apoptosis. Mitochondrial depolarization in the absence of cytochrome c release. J Biol Chem 2000;275:32089-97.
12. Decker RH, Dai Y, Grant S. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in human leukemia cells (U937) through the mitochondrial rather than the receptor-mediated pathway. Cell Death Differ 2001;8:715-24.
13. Chao SH, Price DH. Flavopiridol inactivates P-TEFb and blocks most RNA polymerase II transcription in vivo. J Biol Chem 2001;276:31793-9.
14. Gojo I, Zhang B, Fenton RG. The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of Mcl-1. Clin Cancer Res 2002;8:3527-38.
15. Zhang B, Gojo I, Fenton RG. Myeloid cell factor-1 is a critical survival factor for multiple myeloma. Blood 2002;99:1885-93.
16. Carlson B, Lahusen T, Singh S, et al. Down-regulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol. Cancer Res 1999;59:4634-41.
17. Bergsagel PL, Kuehl WM. Critical roles for immunoglobulin translocations and cyclin D dysregulation in multiple myeloma. Immunol Rev 2003;194:96-104.
18. Semenov I, Akyuz C, Roginskaya V, Chauhan D, Corey SJ. Growth inhibition and apoptosis of myeloma cells by the CDK inhibitor flavopiridol. Leuk Res 2002;26:271-80.
19. Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 1998;281:1322-6.
20. Wei MC, Zong WX, Cheng EH, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001;292:727-30.
21. Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ 2000;7:1166-73.
22. L sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 2001;8:705-11.
23. Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993;75: 241-51.
24. Miyashita T, Reed JC. Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 1993;81:151-7.
25. Karakas T, Maurer U, Weidmann E, Miething CC, Hoelzer D, Bergmann L. High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid leukemia. Ann Oncol 1998;9:129-30.
26. Jansen B, Wacheck V, Heere-Ress E, et al. Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet 2000;356:1728-33.
27. Wang JL, Liu D, Zhang ZJ, et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci U S A 2000;97:7124-9.
28. Yamaguchi H, Paranawithana SR, Lee MW, Huang Z, Bhalla KN, Wang HG. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Res 2002;62:466-71.
29. Milella M, Estrov Z, Kornblau SM, et al. Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia. Blood 2002;99:3461-4.
30. Pettersson M, Jernberg-Wiklund H, Larsson LG, et al. Expression of the bcl-2 gene in human multiple myeloma cell lines and normal plasma cells. Blood 1992;79:495-502.
31. Moalli PA, Pillay S, Weiner D, Leikin R, Rosen ST. A mechanism of resistance to glucocorticoids in multiple myeloma: transient expression of a truncated glucocorticoid receptor mRNA. Blood 1992;79:213-22.
32. Dai Y, Landowski TH, Rosen ST, Dent P, Grant S. Combined treatment with the checkpoint abrogator UCN-01 and MEK1/2 inhibitors potently induces apoptosis in drug-sensitive and -resistant myeloma cells through an IL-6-independent mechanism. Blood 2002;100: 3333-43.
33. Dalton WS, Durie BG, Alberts DS, Gerlach JH, Cress AE. Characterization of a new drug-resistant human myeloma cell line that expresses P-glycoprotein. Cancer Res 1986;46:5125-30.
34. Pei XY, Dai Y, Grant S. The proteasome inhibitor bortezomib promotes mitochondrial injury and apoptosis induced by the small molecule Bcl-2 inhibitor HA14-1 in multiple myeloma cells. Leukemia 2003;17:2036-45.
35. Dai Y, Yu C, Singh V, et al. Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells. Cancer Res 2001;61:5106-15.
36. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
37. Lichtenstein A, Tu Y, Fady C, Vescio R, Berenson J. Interleukin-6 inhibits apoptosis of malignant plasma cells. Cell Immunol 1995;162:248-55.
38. Hazlehurst LA, Enkemann SA, Beam CA, et al. Genotypic and phenotypic comparisons of de novo and acquired melphalan resistance in an isogenic multiple myeloma cell line model. Cancer Res 2003;63:7900-6.
39. Tong AW, Lee J, Wang RM, et al. Elimination of chemoresistant multiple myeloma clonogenic colony-forming cells by combined treatment with a plasma cell-reactive monoclonal antibody and a P-glycoprotein-reactive monoclonal antibody. Cancer Res 1989;49:4829-34.
40. Yin DX, Schimke RT. BCL-2 expression delays drug-induced apoptosis but does not increase clonogenic survival after drug treatment in HeLa cells. Cancer Res 1995;55:4922-8.
41. Liang Y, Nylander KD, Yan C, Schor NF. Role of caspase 3-dependent Bcl-2 cleavage in potentiation of apoptosis by Bcl-2. Mol Pharmacol 2002;61:142-9.
42. Wolter KG, Hsu Y-T, Smith CL, Nechushtan A, Xi X-G, Youle RJ. Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol 1997;139:1281-92.
43. Troussard X, Avet-Loiseau H, Macro M, et al. Cyclin D1 expression in patients with multiple myeloma. Hematol J 2000;1:181-5.
44. Jourdan M, Veyrune JL, Vos JD, Redal N, Couderc G, Klein B. A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells. Oncogene 2003;22:2950-9.
45. Bennett BL, Sasaki DT, Murray BW, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A 2001; 98:13681-6.
46. An J, Chen Y, Huang Z. Critical upstream signals of cytochrome c release induced by a novel Bcl-2 inhibitor. J Biol Chem 2004;279:19133-40.
47. Lickliter JD, Wood NJ, Johnson L, et al. HA14-1 selectively induces apoptosis in Bcl-2-overexpressing leukemia/lymphoma cells, and enhances cytarabine-induced cell death. Leukemia 2003;17:2074-80.
48. Nechushtan A, Smith CL, Hsu YT, Youle RJ. Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J 1999; 18:2330-41.
49. Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13:1899-911.
50. Mitsiades N, Mitsiades CS, Poulaki V, et al. Biologic sequelae of nuclear factor-κB blockade in multiple myeloma: therapeutic applications. Blood 2002;99:4079-86.
51. Takada Y, Aggarwal BB. Flavopiridol inhibits NF-κB activation induced by various carcinogens and inflammatory agents through inhibition of IκBα kinase and p65 phosphorylation: abrogation of cyclin D1, cyclooxygenase-2, and matrix metalloprotease-9. J Biol Chem 2004;279:4750-9.
52. Tang L, Boise LH, Dent P, Grant S. Potentiation of 1-β-D-arabinofuranosylcytosine-mediated mitochondrial damage and apoptosis in human leukemia cells (U937) overexpressing bcl-2 by the kinase inhibitor 7-hydroxystaurosporine (UCN-01). Biochem Pharmacol 2000;60: 1445-56.
53. Podar K, Tai YT, Cole CE, et al. Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells. J Biol Chem 2003;278:5794-801.
54. 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;111:626-34.
55. Honemann D, Chatterjee M, Savino R, et al. The IL-6 receptor antagonist SANT-7 overcomes bone marrow stromal cell-mediated drug resistance of multiple myeloma cells. Int J Cancer 2001;93:674-80.
56. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995;270:1326-31.
57. Tournier C, Hess P, Yang DD, et al. Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 2000;288:870-4.
58. Yamamoto K, Ichijo H, Korsmeyer SJ. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 1999;19:8469-78.
59. Inoshita S, Takeda K, Hatai T, et al. Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress. J Biol Chem 2002;277:43730-4.
60. Zhang Y, Chen F. Reactive oxygen species (ROS), troublemakers between nuclear factor-κB (NF-κB) and c-Jun NH(2)-terminal kinase (JNK). Cancer Res 2004;64:1902-5.
61. Voehringer DW, McConkey DJ, McDonnell TJ, Brisbay S, Meyn RE. Bcl-2 expression causes redistribution of glutathione to the nucleus. Proc Natl Acad Sci U S A 1998;95:2956-60.
62. Shangary S, Johnson DE. Recent advances in the development of anticancer agents targeting cell death inhibitors in the Bcl-2 protein family. Leukemia 2003;17:1470-81.
63. Schimmer AD, Welsh K, Pinilla C, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 2004;5:25-35.