Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2 as a chemosensitizer in cancer therapy

Cancer Gene Therapy

Volumn 14, Issue 1, 2007, Pages 1-11

  Kim, R ^a   Emi, M ^a   Matsuura, K ^a   Tanabe, K ^a  

^a HIROSHIMA UNIVERSITY   (Japan)

Author keywords

Antisense; Antisense effect; Bcl 2; Chemosensitizer; Nonantisense effect

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGODEOXYNUCLEOTIDE; BECLIN 1; CISPLATIN; CPG OLIGODEOXYNUCLEOTIDE; CYCLOPHOSPHAMIDE; CYTARABINE; DACARBAZINE; DAUNORUBICIN; DEXAMETHASONE; DOCETAXEL; FLUDARABINE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; GEMTUZUMAB OZOGAMICIN; IRINOTECAN; OBLIMERSEN; OXALIPLATIN; PACLITAXEL; PROTEIN BCL 2; REACTIVE OXYGEN METABOLITE; THALIDOMIDE; TUMOR SUPPRESSOR PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; APOPTOSIS; AUTOPHAGY; CANCER GENE THERAPY; CHEMOSENSITIZATION; CHEMOTHERAPY INDUCED EMESIS; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONTINUOUS INFUSION; CPG ISLAND; DIARRHEA; DOWN REGULATION; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FEVER; DRUG INTERMITTENT THERAPY; FATIGUE; FEBRILE NEUTROPENIA; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNOSTIMULATION; LUNG NON SMALL CELL CANCER; MELANOMA; MONOTHERAPY; MULTIPLE MYELOMA; NAUSEA; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SOLID TUMOR; STOMACH CANCER; TUMOR CELL;

CLINICAL TRIALS; HUMANS; NEOPLASMS; OLIGONUCLEOTIDES, ANTISENSE; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 33845654040     PISSN: 09291903     EISSN: 14765500     Source Type: Journal    
DOI: 10.1038/sj.cgt.7700986     Document Type: Review

References (77)

1. Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985; 228: 1440-1443.
2. Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988; 335: 440-442.
3. Perego P, Righetti SC, Supino R, Delia D, Caserini C, Carenini N et al. Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines. Apoptosis 1997; 2: 540-548.
4. Rudin CM, Yang Z, Schumaker LM, VanderWeele DJ, Newkirk K, Egorin MJ et al. Inhibition of glutathione synthesis reverses Bcl-2-mediated cisplatin resistance. Cancer Res 2003; 63: 312-318.
5. Reed JC. Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies. Semin Hematol 1997; 34(4 Suppl 5): 9-19.
6. Biroccio A, Del Bufalo D, Fanciulli M, Bruno T, Zupi G, Floridi A. bcl-2 inhibits mitochondrial metabolism and lonidamine-induced apoptosis in adriamycin-resistant MCF7 cells. Int J Cancer 1999; 82: 125-130.
7. Ushmorov A, Ratter F, Lehmann V, Droge W, Schirrmacher V, Umansky V. Nitric-oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome c release. Blood 1999; 93: 2342-2352.
8. Hua C, Raffeld M, Ko HS, Fast P, Bakhshi A, Cossman J. Mechanism of bcl-2 activation in human follicular lymphoma. Oncogene 1990; 5: 233-235.
9. Schimmer AD, Munk-Pedersen I, Minden MD, Reed JC. Bcl-2 and apoptosis in chronic lymphocytic leukemia. Curr Treat Options Oncol 2003; 4: 211-218.
10. Coultas L, Strasser A. The role of the Bcl-2 protein family in cancer. Semin Cancer Biol 2003; 13: 115-123.
11. Chanan-Khan A. Bcl-2 antisense therapy in B-cell malignancies. Blood Rev 2005; 19: 213-221.
12. Armstrong JS. Mitochondria: a target for cancer therapy. Br J Pharmacol 2005; 147: 239-248.
13. Lucken-Ardjomande S, Martinou JC. Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane. C R Biol 2005; 328: 616-631.
14. Hail Jr N. Mitochondria: a novel target for the chemoprevention of cancer. Apoptosis 2005; 10: 687-705.
15. Kim R. Recent advances in understanding the cell death pathways activated by anticancer therapy. Cancer 2005; 103: 1551-1560.
16. Bouchier-Hayes L, Lartigue L, Newmeyer DD. Mitochondria: pharmacological manipulation of cell death. J Clin Invest 2005; 115: 2640-2647.
17. Mikhailov V, Mikhailova M, Degenhardt K, Venkatachalam MA, White E, Saikumar P. Association of Bax and Bak homo-oligomers in mitochondria. Bax requirement for Bak reorganization and cytochrome c release. J Biol Chem 2003; 278: 5367-5376.
18. Tolcher AW. Targeting Bcl-2 protein expression in solid tumors and hematologic malignancies with antisense oligonucleotides. Clin Adv Hematol Oncol 2005; 3: 635-642, 662.
19. De Cesare M, Perego P, Righetti SC, Pratesi G, Carenini N, Rivoltini L et al. Enhanced antitumour efficacy of gimatecan in combination with Bcl-2 antisense oligonucleotide in human melanoma xenografts. Eur J Cancer 2005; 41: 1213-1222.
20. Emi M, Kim R, Tanabe K, Uchida Y, Toge T. Targeted therapy against Bcl-2-related proteins in breast cancer cells. Breast Cancer Res 2005; 7: R940-R952.
21. Kim R, Emi M, Tanabe K, Toge T. Preclinical evaluation of antisense bcl-2 as a chemosensitizer for patients with gastric carcinoma. Cancer 2004; 101: 2177-2186.
22. Lopes de Menezes DE, Hudon N, McIntosh N, Mayer LD. Molecular and pharmacokinetic properties associated with the therapeutics of bcl-2 antisense oligonucleotide G3139 combined with free and liposomal doxorubicin. Clin Cancer Res 2000; 6: 2891-2902.
23. Marcucci G, Byrd JC, Dai G, Klisovic MI, Kourlas PJ, Young DC et al. Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia. Blood 2003; 101: 425-432.
24. Tolcher AW, Kuhn J, Schwartz G, Patnaik A, Hammond LA, Thompson I et al. A phase I pharmacokinetic and biological correlative study of oblimersen sodium (genasense, g3139), an antisense oligonucleotide to the bcl-2 mRNA, and of docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer Res 2004; 10: 5048-5057.
25. Marshall J, Chen H, Yang D, Figueira M, Bouker KB, Ling Y et al. A phase Itrial of a Bcl-2 antisense (G3139) and weekly docetaxel in patients with advanced breast cancer and other solid tumors. Ann Oncol 2004; 15: 1274-1283.
26. Rudin CM, Otterson GA, Mauer AM, Villalona-Calero MA, Tomek R, Prange B et al. A pilot trial of G3139, a bcl-2 antisense oligonucleotide, and paclitaxel in patients with chemorefractory small-cell lung cancer. Ann Oncol 2002; 13: 539-545.
27. Rudin CM, Kozloff M, Hoffman PC, Edelman MJ, Karnauskas R, Tomek R et al. Phase Istudy of G3139, a bcl-2 antisense oligonucleotide, combined with carboplatin and etoposide in patients with small-cell lung cancer. J Clin Oncol 2004; 22: 1110-1117.
28. Morris MJ, Tong WP, Cordon-Cardo C, Drobnjak M, Kelly WK, Slovin SF et al. Phase Itrial of BCL-2 antisense oligonucleotide (G3139) administered by continuous intravenous infusion in patients with advanced cancer. Clin Cancer Res 2002; 8: 679-683.
29. Chi KN, Gleave ME, Klasa R, Murray N, Bryce C, Lopes de Menezes DE et al. A phase I dose-finding study of combined treatment with an antisense Bcl-2 oligonucleotide (Genasense) and mitoxantrone in patients with metastatic hormone-refractory prostate cancer. Clin Cancer Res 2001; 7: 3920-3927.
30. Kirkwood JM, Bedikian AY, Millward MJ, Conry RM, Gore ME, Pehamberger HE et al. Long-term survival results of randomized multinational phase 3 trial of dacarbazine (DTIC) with or without Bcl-2 antisense (oblimersen sodium) in patients with advanced malignant melanoma. Proc Annu Meeting ASCO 2005; 23(16S): 711s.
31. Stein CA, Benimetskaya L, Mani S. Antisense strategies for oncogene inactivation. Semin Oncol 2005; 32: 563-572.
32. Letai A. Pharmacological manipulation of Bcl-2 family members to control cell death. J Clin Invest 2005; 115: 2648-2655.
33. Wacheck V, Krepler C, Strommer S, Heere-Ress E, Klem R, Pehamberger H et al. Antitumor effect of G3139 Bcl-2 antisense oligonucleotide is independent of its immune stimulation by CpG motifs in SCID mice. Antisense Nucleic Acid Drug Dev 2002; 12: 359-367.
34. Badros AZ, Goloubeva O, Rapoport AP, Ratterree B, Gahres N, Meisenberg B et al. Phase II study of G3139, a Bcl-2 antisense oligonucleotide, in combination with dexamethasone and thalidomide in relapsed multiple myeloma patients. J Clin Oncol 2005; 23: 4089-4099.
35. Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000; 102: 33-42.
36. Song Z, Yao X, Wu M. Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. J Biol Chem 2003; 278: 23130-23140.
37. Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y. Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 2000; 406: 855-862.
38. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999; 397: 441-446.
39. Clement MV, Hirpara JL, Pervaiz S. Decrease in intracellular superoxide sensitizes Bcl-2-overexpressing tumor cells to receptor and drug-induced apoptosis independent of the mitochondria. Cell Death Differ 2003; 10: 1273-1285.
40. Lai JC, Benimetskaya L, Santella RM, Wang Q, Miller PS, Stein CA. G3139 (oblimersen) may inhibit prostate cancer cell growth in a partially bis-CpG-dependent non-antisense manner. Mol Cancer Ther 2003; 2: 1031-1043.
41. Raffo A, Lai JC, Stein CA, Miller P, Scaringe S, Khvorova A et al. Antisense RNA down-regulation of bcl-2 expression in DU145 prostate cancer cells does not diminish the cytostatic effects of G3139 (Oblimersen). Clin Cancer Res 2004; 10: 3195-3206.
42. Kolenko VM, Uzzo RG, Bukowski R, Finke JH. Caspase-dependent and -independent death pathways in cancer therapy. Apoptosis 2000; 5: 17-20.
43. Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest 2005; 115: 2679-2688.
44. Mizushima N. The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ 2005; 12: 1535-1541.
45. Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E et al. Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 1999; 59: 59-65.
46. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672-676.
47. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005; 122: 927-939.
48. Saeki K, Yuo A, Okuma E, Yazaki Y, Susin SA, Kroemer G et al. Bcl-2 down-regulation causes autophagy in a caspase-independent manner in human leukemic HL60 cells. Cell Death Differ 2000; 7: 1263-1269.
49. Tracey L, Perez-Rosado A, Artiga MJ, Camacho FI, Rodriguez A, Martinez N et al. Expression of the NF-kappaB targets BCL2 and BIRC5/Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively. J Pathol 2005; 206: 123-134.
50. Choi J, Choi K, Benveniste EN, Hong YS, Lee JH, Kim J et al. Bcl-2 promotes invasion and lung metastasis by inducing matrix metalloproteinase-2. Cancer Res 2005; 65: 5554-5560.
51. Biroccio A, Candiloro A, Mottolese M, Sapora O, Albini A, Zupi G et al. Bcl-2 overexpression and hypoxia synergistically act to modulate vascular endothelial growth factor expression and in vivo angiogenesis in a breast carcinoma line. FASEB J 2000; 14: 652-660.
52. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1996; 2: 1096-1103.
53. Jahrsdorfer B, Jox R, Muhlenhoff L, Tschoep K, Krug A, Rothenfusser S et al. Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN. J Leukoc Biol 2002; 72: 83-92.
54. Wiemann B, Starnes CO. Coley's toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol Ther 1994; 64: 529-564.
55. Tokunaga T, Yamamoto H, Shimada S, Abe H, Fukuda T, Fujisawa Y et al. Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity. J Natl Cancer Inst 1984; 72: 955-962.
56. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374: 546-549.
57. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H et al. A Toll-like receptor recognizes bacterial DNA. Nature 2000; 408: 740-745.
58. Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 2002; 20: 709-760.
59. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol 2005; 23: 515-548.
60. Vollmer J, Weeratna R, Payette P, Jurk M, Schetter C, Laucht M et al. Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur J Immunol 2004; 34: 251-262.
61. Duramad O, Fearon KL, Chan JH, Kanzler H, Marshall JD, Coffman RL et al. IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences. Blood 2003; 102: 4487-4492.
62. Kim R, Emi M, Tanabe K. Cancer cell immune escape and tumor progression by exploitation of anti-inflammatory and pro-inflammatory responses. Cancer Biol Ther 2005; 4: 924-933.
63. Zou W, Machelon V, Coulomb-L'Hermin A, Borvak J, Nome F, Isaeva T et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 2001; 7: 1339-1346.
64. Nowak AK, Lake RA, Marzo AL, Scott B, Heath WR, Collins EJ et al. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J Immunol 2003; 170: 4905-4913.
65. Serafini P, De Santo C, Marigo I, Cingarlini S, Dolcetti L, Gallina G et al. Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 2004; 53: 64-72.
66. Kusmartsev S, Gabrilovich DI. Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother 2002; 51: 293-298.
67. Benimetskaya L, Wittenberger T, Stein CA, Hofmann HP, Weller C, Lai JC et al. Changes in gene expression induced by phosphorothioate oligodeoxynucleotides (including G3139) in PC3 prostate carcinoma cells are recapitulated at least in part by treatment with interferon-beta and -gamma. Clin Cancer Res 2004; 10: 3678-3688.
68. Kaubisch A, Wu Y-H, Wadler S. Phase I/II study of genasense (G3139) in combination with cisplatin and fluorouracil in patients with advanced esophageal, gastroesophageal junction and gastric cancer. Proc Annu Meeting ASCO 2005; 884s.
69. Mays TA, Mita AC, Takimoto C, Petro D, Egorin MJ, Patnaik A et al. Bcl-2 biomodulation with oblimersen sodium in combination with FOLFOX4 chemotherapy: a phase Istudy in metastatic colon carcinoma. Proc Annu Meeting ASCO 2005; 24: 231s.
70. Mita MM, Ochoa L, Rowinsky EK, Kuhn J, Schwartz G, Hammond LA et al. A phase I, pharmacokinetic and biologic correlative study of oblimersen sodium (Genasense™, G3139) and irinotecan in patients with metastatic colorectal cancer. Ann Oncol 2006; 17: 313-321.
71. Fisher G, Advani R, Wakelee H, Jacobs C, Gladysheva K, Fitzgerald AM et al. A phase Itrial of oblimersen and gemcitabine in refractory and advanced malignancies. Proc Annu Meeting ASCO 2005; 23(16S): 234s.
72. Tolcher AW, Chi K, Kuhn J, Gleave M, Patnaik A, Takimoto C et al. A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer Res 2005; 11: 3854-3861.
73. Winegarden JD, Mauer AM, Otterson GA, Rudin CM, Villalona-Calero MA, Lanzotti VJ et al. A phase II study of oxaliplatin and paclitaxel in patients with advanced non-small-cell lung cancer. Ann Oncol 2004; 15: 915-920.
74. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T et al. Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic applications. Blood 2002; 99: 4079-4086.
75. Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC. Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci USA 1998; 95: 4997-5002.
76. van de Donk NW, de Weerdt O, Veth G, Eurelings M, van Stralen E, Frankel SR et al. G3139, a Bcl-2 antisense oligodeoxynucleotide, induces clinical responses in VAD refractory myeloma. Leukemia 2004; 18: 1078-1084.
77. Sawada S, Mese H, Sasaki A, Yoshioka N, Matsumura T. Combination chemotherapy of paclitaxel and cisplatin induces apoptosis with Bcl-2 phosphorylation in a cisplatin-resistant human epidermoid carcinoma cell line. Cancer Chemother Pharmacol 2003; 51: 505-511.