RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses

Molecular Cancer Therapeutics

Volumn 9, Issue 11, 2010, Pages 3041-3051

  Saha, Manujendra N ^a,b   Jiang, Hua ^a,b,d   Mukai, Asuka ^a,b   Chang, Hong ^a,b,c  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c TORONTO GENERAL HOSPITAL   (Canada)

^d SHANGHAI CHILDREN S MEDICAL CENTER   (China)

Author keywords

[No Author keywords available]

Indexed keywords

5,5' (2,5 FURANDIYL)BIS 2 THIOPHENEMETHANOL; [2,5 BIS (5 HYDROXYMETHYL 2 THIENYL)FURAN]; ANTINEOPLASTIC AGENT; APOPTOSIS REPRESSOR WITH CASPASE RECRUITMENT DOMAIN; NUTLIN 3; PROTEIN MCL 1; PROTEIN MDM2; PROTEIN P53; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CYTOTOXICITY; DOWN REGULATION; DRUG ACTIVITY; DRUG POTENTIATION; DRUG STRUCTURE; ENZYME ACTIVATION; GENE EXPRESSION PROFILING; GENE TARGETING; HUMAN; HUMAN CELL; MULTIPLE MYELOMA; MYELOMA CELL; PRIORITY JOURNAL; UPREGULATION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CASPASES; CELL PROLIFERATION; CELLS, CULTURED; CYTOTOXINS; DNA-BINDING PROTEINS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; DRUG SYNERGISM; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMIDAZOLES; MICROARRAY ANALYSIS; MULTIPLE MYELOMA; NEOPLASM PROTEINS; PIPERAZINES; SIGNAL TRANSDUCTION; TIME FACTORS; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 78649645749     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-10-0471     Document Type: Article

References (40)

1. Salmon SE, Dalton WS, Grogan TM, et al. Multidrug-resistant myeloma: laboratory and clinical effects of verapamil as a chemosensitizer. Blood 1991;78:44-50.
2. Sonneveld P. Drug resistance in multiple myeloma. Pathol Biol (Paris) 1999;47:182-7.
3. Covelli A. Modulation of multidrug resistance (MDR) in hematological malignancies. Ann Oncol 1999;10 Suppl6:53-9.
4. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352:2487-98.
5. Oren M. Decision making by p53: life, death and cancer. Cell Death Differ 2003;10:431-42. (Pubitemid 36626355)
6. Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 2002;19:607-14. (Pubitemid 34556481)
7. Avet-Loiseau H, Li JY, Godon C, et al. p53 deletion is not a frequent event in multiple myeloma. Br J Haematol 1999;106:717-9.
8. Chng WJ, Price-Troska T, Gonzalea-Paz N, et al. Clinical significance of TP53 mutation in myeloma. Leukemia 2007;13:582-4.
9. Chang H, Qi C, Yi Q, Reece D, Stewart AK. p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. Blood 2005;105:358-60.
10. Chene P. Inhibiting the p53-2 interaction: an important target for cancer therapy. Nat Rev Cancer 2003;3:102-9. (Pubitemid 37328877)
11. Prives C. Signaling to p53: breaking the MDM2-53 circuit. Cell 1998;95:5-8. (Pubitemid 28458016)
12. Fang S, Jensen JP, Ludwig RL, Vousden KH, Weisman AM. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 2000;275:8945-51. (Pubitemid 30180252)
13. Vassilev LT. MDM2 inhibitors for cancer therapy. Trends Mol Med 2007;13:23-31.
14. Saha MN, Micallef J, Qiu L, Chang H. Pharmacological activation of the p53 pathway in haematological malignancies. J Clin Pathol 2010;63:204-9.
15. Stühmer T, Chatterjee M, Hildebrandt M, et al. Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma. Blood 2005;106:3609-17.
16. Ooi MG, Hayden PJ, Kotoula V, et al. Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib. Clin Cancer Res 2009;15:7153-60.
17. Saha MN, Jiang H, Chang H. Molecular mechanisms of nutlin-induced apoptosis in multiple myeloma: evidence for p53-transcription-dependent and -independent pathways. Cancer Biol Ther 2010;10:567-78.
18. Saha MN, Jiang H, Jayakar J, Reece D, Branch DR, Chang H. MDM2 antagonist nutlin plus proteasome inhibitor velcade combination displays a synergistic anti-myeloma activity. Cancer Biol Ther 2010;9:936-44.
19. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004;303:844-8.
20. Issaeva N, Bozko P, Enge M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumours. Nat Med 2004;12:1321-8.
21. Kojima K, konopleva M, Samudio IJ, et al. MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy. Blood 2005;106:3150-9.
22. Secchiero P, Barbarotto E, Tiribelli M, et al. Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood 2006;107:4122-9.
23. Drakos E, Thomaids A, Medeiros LJ, et al. Inhibition of p53-murine double minute-2 interaction by nutlin-3A stabilizes p53 and induces cell cycle arrest and apoptosis in Hodgkin lymphoma. Clin Cancer Res 2007;13:3380-7.
24. Gu L, Zhu N, Findley HW, Zhou M. MDM2 antagonist nutlin-3 is a potent inducer of apoptosis in pediatric acute lymphoblastic leukemia cells with wild-type p53 and over expression of MDM2. Leukemia 2008;22:730-9.
25. Rinaldo C, Prodosmo A, Siepi F, et al. HIPK2 regulation by MDM2 determines tumor cell response to the p53-reactivating drugs nutlin-3 and RITA. Cancer Res 2009;69:6241-8.
26. Enge M, Bao W, Hedström E, Jackson SP, Moumen A, Selivanova G. MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53. Cancer Cell 2009;15:171-83.
27. Grinkevich VV, Nikulenkov F, Shi Y, et al. Ablation of Key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis. Cancer Cell 2009;15:441-53.
28. Zhao CY, Szekely L, Bao W, Selivanova G. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation. Cancer Res 2010;70:3372-81.
29. Rivera MI, Stinson SF, Vistica JT, Jorden JL, Kenney S, Sausville EA. Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines. Biochem Pharmacol 1999;57:1283-95.
30. Nieves-Neira W, Rivera MI, Kohlhagen G, et al.DNAprotein cross-links produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells. Mol Pharmacol 1999;56:478-84.
31. Nahi H, Selivanova G, Lehmann S, et al. Mutated and non-mutated TP53 as targets in the treatment of leukaemia. Br J Haematol 2008;141:445-53.
32. Buzzeo R, Enkemann S, Nimmanapalli R, et al. Characterization of a R115777-resistant human multiple myeloma cell line with cross-resistance to PS-341. Clin Cancer Res 2005;11:6057-64. (Pubitemid 41170338)
33. Doggrell SA. RITA - a small-molecule anticancer drug that targets p53. Expert Opin Investig Drugs 2005;14:739-42.
34. Baou M, Kohlhaas S, Butterworth M, et al. Role of NOXA and its ubiquitination in proteasome inhibitor-induced apoptosis in chronic lymphocytic leukemia cells. Haematologica 2010;95:1510-8.
35. Inoue S, Riley J, Gant TW, Dyer MJ, Cohen GM. Apoptosis induced by histone deacetylase inhibitors in leukemic cells is mediated by Bim and Noxa. Leukemia 2007;21:1773-82. (Pubitemid 47086766)
36. Gomez-Bougie P, Wuillème-Toumi S, Ménoret E, et al. Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma. Cancer Res 2007;67:5418-24.
37. Derenne S, Monia B, Dean NM, et al. Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood 2002;100:194-9.
38. Yili Y. Targeting the ubiquitin-proteasome system for cancer therapy. Cancer Sci 2009;100:24-28.
39. Sun S, Han J, Ralph WM, Jr., et al. Endoplasmic reticulum stress as a correlate of cytotoxicity in human tumor cells exposed to diindolylmetnane in vitro. Cell Stress Chaperones 2004;9:76-87. (Pubitemid 38429078)
40. Wang Q, Mora-Jensen H, Weniger MA, et al. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci U S A 2009;106:2200-5.