The MDM2-inhibitor Nutlin-3 synergizes with cisplatin to induce p53 dependent tumor cell apoptosis in non-small cell lung cancer

Oncotarget

Volumn 6, Issue 26, 2015, Pages 22666-22679

  Deben, Christophe ^a,b   Wouters, An ^a   Op de Beeck, Ken ^a   van Den Bossche, Jolien ^a   Jacobs, Julie ^a   Zwaenepoel, Karen ^b   Peeters, Marc ^a,b   Van Meerbeeck, Jan ^b   Lardon, Filip ^a   Rolfo, Christian ^b   Deschoolmeester, Vanessa ^a,b   Pauwels, Patrick ^a,b  

^a UNIVERSITY OF ANTWERP   (Belgium)

^b ANTWERP UNIVERSITY HOSPITAL   (Belgium)

Author keywords

Cisplatin; MDM2; NSCLC; P53; Synergism

Indexed keywords

CISPLATIN; NUTLIN 3; PROTEIN BAX; PROTEIN MDM2; PROTEIN P21; PROTEIN P53; PUMA PROTEIN; ANTINEOPLASTIC AGENT; IMIDAZOLE DERIVATIVE; MDM2 PROTEIN, HUMAN; MESSENGER RNA; PIPERAZINE DERIVATIVE; TP53 PROTEIN, HUMAN;

APOPTOSIS; ARTICLE; CELL CYCLE G0 PHASE; CELL MEDIATED CYTOTOXICITY; CELL SURVIVAL; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE RESPONSE; DRUG POTENTIATION; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; MONOTHERAPY; NON SMALL CELL LUNG CANCER; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY MECHANISM; TREATMENT RESPONSE; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CARCINOMA, NON-SMALL-CELL LUNG; DRUG ADMINISTRATION; DRUG EFFECTS; GENETICS; LUNG NEOPLASMS; METABOLISM; PATHOLOGY; TRANSCRIPTION INITIATION; TUMOR CELL LINE;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CISPLATIN; DRUG ADMINISTRATION SCHEDULE; DRUG SYNERGISM; HUMANS; IMIDAZOLES; LUNG NEOPLASMS; PIPERAZINES; PROTO-ONCOGENE PROTEINS C-MDM2; RNA, MESSENGER; TRANSCRIPTIONAL ACTIVATION; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84941203172     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.4433     Document Type: Article

References (36)

1. Brown CJ, Lain S, Verma CS, Fersht AR and Lane DP. Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer. 2009; 9:862-873.
2. Dickens MP, Fitzgerald R and Fischer PM. Small-molecule inhibitors of MDM2 as new anticancer therapeutics. Seminars in cancer biology. 2010; 20:10-18.
3. Shangary S and Wang S. Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy. Annual review of pharmacology and toxicology. 2009; 49:223-241.
4. Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, Myklebost O, Heimbrook DC and Vassilev LT. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103:1888-1893.
5. Vassilev LT. Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics. Cell Cycle. 2004; 3:419-421.
6. Momand J, Jung D, Wilczynski S and Niland J. The MDM2 gene amplification database. Nucleic acids research. 1998; 26:3453-3459.
7. Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G and Levine AJ. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004; 119:591-602.
8. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N and Liu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004; 303:844-848.
9. Ohnstad HO, Paulsen EB, Noordhuis P, Berg M, Lothe RA, Vassilev LT and Myklebost O. MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines. BMC cancer. 2011; 11:211:211-211.
10. Basu A and Krishnamurthy S. Cellular responses to Cisplatin-induced DNA damage. Journal of nucleic acids. 2010; 2010.
11. Mir R, Tortosa A, Martinez-Soler F, Vidal A, Condom E, Perez-Perarnau A, Ruiz-Larroya T, Gil J and Gimenez-Bonafe P. Mdm2 antagonists induce apoptosis and synergize with cisplatin overcoming chemoresistance in TP53 wild-type ovarian cancer cells. International journal of cancer Journal international du cancer. 2013; 132:1525-1536.
12. Carvajal D, Tovar C, Yang H, Vu BT, Heimbrook DC and Vassilev LT. Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors. Cancer research. 2005; 65:1918-1924.
13. Tokalov SV and Abolmaali ND. Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment. BMC cancer. 2010; 10:57.
14. Shen HC, Dong W, Gao DW, Wang GH, Ma GY, Liu Q and Du JJ. MDM2 antagonist Nutlin-3a protects wild-type p53 cancer cells from paclitaxel. Chinese Sci Bull. 2012; 57:1007-1012.
15. Jiang M, Pabla N, Murphy RF, Yang T, Yin XM, Degenhardt K, White E and Dong Z. Nutlin-3 protects kidney cells during cisplatin therapy by suppressing Bax/Bak activation. The Journal of biological chemistry. 2007; 282:2636-2645.
16. Fan S, Smith ML, Rivet DJ, 2nd, Duba D, Zhan Q, Kohn KW, Fornace AJ, Jr. and O'Connor PM. Disruption of p53 function sensitizes breast cancer MCF-7 cells to cisplatin and pentoxifylline. Cancer research. 1995; 55:1649-1654.
17. Hoe KK, Verma CS and Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nature reviews Drug discovery. 2014; 13:217-236.
18. Pabla N, Huang S, Mi QS, Daniel R and Dong Z. ATRChk2 signaling in p53 activation and DNA damage response during cisplatin-induced apoptosis. The Journal of biological chemistry. 2008; 283:6572-6583.
19. Ma X, Rousseau V, Sun H, Lantuejoul S, Filipits M, Pirker R, Popper H, Mendiboure J, Vataire AL, Le Chevalier T, Soria JC, Brambilla E, Dunant A, Hainaut P and group IABw. Significance of TP53 mutations as predictive markers of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer. Molecular oncology. 2014; 8:555-564.
20. Tsao MS, Aviel-Ronen S, Ding K, Lau D, Liu N, Sakurada A, Whitehead M, Zhu CQ, Livingston R, Johnson DH, Rigas J, Seymour L, Winton T and Shepherd FA. Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2007; 25:5240-5247.
21. Kandioler D, Stamatis G, Eberhardt W, Kappel S, Zochbauer-Muller S, Kuhrer I, Mittlbock M, Zwrtek R, Aigner C, Bichler C, Tichy V, Hudec M, Bachleitner T, End A, Muller MR, Roth E, et al. Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer. The Journal of thoracic and cardiovascular surgery. 2008; 135:1036-1041.
22. Miyachi M, Kakazu N, Yagyu S, Katsumi Y, Tsubai-Shimizu S, Kikuchi K, Tsuchiya K, Iehara T and Hosoi H. Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells. Clinical cancer research: an official journal of the American Association for Cancer Research. 2009; 15:4077-4084.
23. Villalonga-Planells R, Coll-Mulet L, Martinez-Soler F, Castano E, Acebes JJ, Gimenez-Bonafe P, Gil J and Tortosa A. Activation of p53 by nutlin-3a induces apoptosis and cellular senescence in human glioblastoma multiforme. PloS one. 2011; 6:e18588.
24. Benchimol S. p53-dependent pathways of apoptosis. Cell death and differentiation. 2001; 8:1049-1051.
25. Lambert JM, Gorzov P, Veprintsev DB, Soderqvist M, Segerback D, Bergman J, Fersht AR, Hainaut P, Wiman KG and Bykov VJ. PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer cell. 2009; 15:376-388.
26. Lau LM, Nugent JK, Zhao X and Irwin MS. HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function. Oncogene. 2008; 27:997-1003.
27. Ambrosini G, Sambol EB, Carvajal D, Vassilev LT, Singer S and Schwartz GK. Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1. Oncogene. 2007; 26:3473-3481.
28. Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J, Heil F, Rueger R, Graves B, Ding M, Geho D, Middleton SA, Vassilev LT, Nichols GL and Bui BN. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-ofmechanism study. The lancet oncology. 2012; 13:1133-1140.
29. Higgins B, Kelli G, Walz A, Tovar C, Filipovic Z, Hussain S, Lee E, Kolinsky K, Tannu S, Adames V, Garrido R, Linn M, Meille C, Heimbrook D, Vassilev LT and Packman K. Preclinical optimization of MDM2 antagonist scheduling for cancer treatment by using a model-based approach. Clinical cancer research: an official journal of the American Association for Clin Cancer Res. 2014; 20:3742-52.
30. Tovar C, Graves B, Packman K, Filipovic Z, Higgins B, Xia M, Tardell C, Garrido R, Lee E, Kolinsky K, To KH, Linn M, Podlaski F, Wovkulich P, Vu B and Vassilev LT. MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models. Cancer research. 2013; 73:2587-2597.
31. Ohnstad HO, Castro R, Sun J, Heintz KM, Vassilev LT, Bjerkehagen B, Kresse SH, Meza-Zepeda LA and Myklebost O. Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma. Cancer. 2013; 119:1013-1022.
32. Pauwels B, Korst AE, de Pooter CM, Pattyn GG, Lambrechts HA, Baay MF, Lardon F and Vermorken JB. Comparison of the sulforhodamine B assay and the clonogenic assay for in vitro chemoradiation studies. Cancer chemotherapy and pharmacology. 2003; 51:221-226.
33. Chou TC and Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in enzyme regulation. 1984; 22:27-55.
34. Limame R, Wouters A, Pauwels B, Fransen E, Peeters M, Lardon F, De Wever O and Pauwels P. Comparative analysis of dynamic cell viability, migration and invasion assessments by novel real-time technology and classic endpoint assays. PloS one. 2012; 7:e46536.
35. Pauwels B, Korst AE, Andriessen V, Baay MF, Pattyn GG, Lambrechts HA, Pooter CM, Lardon F and Vermorken JB. Unraveling the mechanism of radiosensitization by gemcitabine: the role of TP53. Radiation research. 2005; 164:642-650.
36. Pauwels B, Korst AE, Pattyn GG, Lambrechts HA, Van Bockstaele DR, Vermeulen K, Lenjou M, de Pooter CM, Vermorken JB and Lardon F. Cell cycle effect of gemcitabine and its role in the radiosensitizing mechanism in vitro. International journal of radiation oncology, biology, physics. 2003; 57:1075-1083.