Inauhzin sensitizes p53-dependent cytotoxicity and tumor suppression of chemotherapeutic agents

Neoplasia (United States)

Volumn 15, Issue 5, 2013, Pages 523-534

  Zhang, Yiwei ^a   Zhang, Qi ^a   Zeng, Shelya X ^a   Hao, Qian ^a   Lu, Hua ^a  

^a TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BROXURIDINE; CISPLATIN; DOXORUBICIN; INAUHZIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; P21 ACTIVATED KINASE; PROTEIN P53; UNCLASSIFIED DRUG; 10-(2-(5H-(1,2,4)TRIAZINO(5,6-B)INDOL-3-YLTHIO)BUTANOYL)-10H-PHENOTHIAZINE; INDOLE DERIVATIVE; PHENOTHIAZINE DERIVATIVE; TP53 PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL CULTURE; CELL PROLIFERATION; CELL VIABILITY; CHEMOSENSITIVITY; COLON CANCER; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IN VIVO STUDY; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR GROWTH; TUMOR VOLUME; TUMOR XENOGRAFT; WESTERN BLOTTING; ANIMAL; CELL SURVIVAL; DRUG EFFECTS; DRUG POTENTIATION; DRUG RESISTANCE; DRUG SCREENING; METABOLISM; SCID MOUSE; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CISPLATIN; DOXORUBICIN; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; FEMALE; HUMANS; INDOLES; MICE; MICE, SCID; PHENOTHIAZINES; TUMOR BURDEN; TUMOR SUPPRESSOR PROTEIN P53; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84877031607     PISSN: 15228002     EISSN: 14765586     Source Type: Journal    
DOI: 10.1593/neo.13142     Document Type: Article

References (100)

1. Dy GK and Adjei AA (2008). Systemic cancer therapy: evolution over the last 60 years. Cancer 113, 1857-1887.
2. Boulikas T and Vougiouka M (2003). Cisplatin and platinum drugs at the molecular level (Review). Oncol Rep 10, 1663-1682.
3. Wallace KB (2003). Doxorubicin-induced cardiac mitochondrionopathy. Pharmacol Toxicol 93, 105-115.
4. Gonzales-Vitale JC, Hayes DM, Cvitkovic E, and Sternberg SS (1977). The renal pathology in clinical trials of cis-platinum (II) diamminedichloride. Cancer 39, 1362-1371.
5. Hanigan MH and Devarajan P (2003). Cisplatin nephrotoxicity: molecular mechanisms. Cancer Ther 1, 47-61.
6. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, and Sanders SP (1991). Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 324, 808-815.
7. Zhang YW, Shi J, Li YJ, and Wei L (2009). Cardiomyocyte death in doxorubicininduced cardiotoxicity. Arch Immunol Ther Exp (Warsz) 57, 435-445.
8. Singal PK and Iliskovic N (1998). Doxorubicin-induced cardiomyopathy. NEngl J Med 339, 900-905.
9. Baird RD and Kaye SB (2003). Drug resistance reversal-are we getting closer? Eur J Cancer 39, 2450-2461.
10. Lane D and Levine A (2010). p53 Research: the past thirty years and the next thirty years. Cold Spring Harb Perspect Biol 2, a000893.
11. Leung AK and Sharp PA (2010). MicroRNA functions in stress responses. Mol Cell 40, 205-215.
12. Boominathan L (2010). The guardians of the genome (p53, TA-p73, and TA-p63) are regulators of tumor suppressor miRNAs network. Cancer Metastasis Rev 29, 613-639.
13. Hollstein M, Sidransky D, Vogelstein B, and Harris CC (1991). p53 Mutations in human cancers. Science 253, 49-53.
14. Vogelstein B, Lane D, and Levine AJ (2000). Surfing the p53 network. Nature 408, 307-310.
15. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, and Olivier M (2007). Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 28, 622-629.
16. Zhang Q, Zeng SX, Zhang Y, Zhang Y, Ding D, Ye Q, Meroueh SO, and Lu H (2012). A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med 4, 298-312.
17. Momand J, Zambetti GP, Olson DC, George D, and Levine AJ (1992). The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69, 1237-1245.
18. Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, and Vogelstein B (1993). Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362, 857-860.
19. Kruse JP and Gu W (2009). Modes of p53 regulation. Cell 137, 609-622.
20. Wade M, Wang YV, and Wahl GM (2010). The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol 20, 299-309.
21. Kawai H, Lopez-Pajares V, Kim MM, Wiederschain D, and Yuan ZM (2007). RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity. Cancer Res 67, 6026-6030.
22. Linke K, Mace PD, Smith CA, Vaux DL, Silke J, and Day CL (2008). Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ 15, 841-848.
23. Wu X, Bayle JH, Olson D, and Levine AJ (1993). The p53-mdm-2 autoregulatory feedback loop. Genes Dev 7, 1126-1132.
24. Levine AJ and Oren M (2009). The first 30 years of p53: growing ever more complex. Nat Rev Cancer 9, 749-758.
25. Shangary S and Wang S (2009). Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy. Annu Rev Pharmacol Toxicol 49, 223-241.
26. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, et al. (2004). In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844-848.
27. Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, and Selivanova G (2004). Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med 10, 1321-1328.
28. Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska.Z, Ding K, Wang G, Chen J, et al. (2008). Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci USA 105, 3933-3938.
29. Yang Y, Ludwig RL, Jensen JP, Pierre SA, Medaglia MV, Davydov IV, Safiran YJ, Oberoi P, Kenten JH, Phillips AC, et al. (2005). Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 7, 547-559.
30. Reed D, Shen Y, Shelat AA, Arnold LA, Ferreira AM, Zhu F, Mills N, Smithson DC, Regni CA, Bashford D, et al. (2010). Identification and characterization of the first small molecule inhibitor of MDMX. J Biol Chem 285, 10786-10796.
31. Kobet E, Zeng X, Zhu Y, Keller D, and Lu H (2000). MDM2 inhibits p300-- mediated p53 acetylation and activation by forming a ternary complex with the two proteins. Proc Natl Acad Sci USA 97, 12547-12552.
32. Ito A, Lai CH, Zhao X, Saito S, Hamilton MH, Appella E, and Yao TP (2001). p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J 20, 1331-1340.
33. Gu W and Roeder RG (1997). Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90, 595-606.
34. Li M, Luo J, Brooks CL, and Gu W (2002). Acetylation of p53 inhibits its ubiquitination by Mdm2. J Biol Chem 277, 50607-50611.
35. Ito A, Kawaguchi Y, Lai CH, Kovacs JJ, Higashimoto Y, Appella E, and Yao TP (2002). MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J 21, 6236-6245.
36. Huffman DM, Grizzle WE, Bamman MM, Kim JS, Eltoum IA, Elgavish A, and Nagy TR (2007). SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res 67, 6612-6618.
37. Jung-Hynes B, Nihal M, Zhong W, and Ahmad N (2009). Role of sirtuin histone deacetylase SIRT1 in prostate cancer. A target for prostate cancer management via its inhibition? J Biol Chem 284, 3823-3832.
38. Chen WY, Wang DH, Yen RC, Luo J, Gu W, and Baylin SB (2005). Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNAdamage responses. Cell 123, 437-448.
39. Lain S, Hollick JJ, Campbell J, Staples OD, Higgins M, Aoubala M, McCarthy A, Appleyard V, Murray KE, Baker L, et al. (2008). Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell 13, 454-463.
40. Fraser M, Bai T, and Tsang BK (2008). Akt promotes cisplatin resistance in human ovarian cancer cells through inhibition of p53 phosphorylation and nuclear function. Int J Cancer 122, 534-546.
41. Ali AY, Abedini MR, and Tsang BK (2012). The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation. Oncogene 31, 2175-2186.
42. Fraser M, Leung BM, Yan X, Dan HC, Cheng JQ, and Tsang BK (2003). p53 is a determinant of X-linked inhibitor of apoptosis protein/Akt-mediated chemoresistance in human ovarian cancer cells. Cancer Res 63, 7081-7088.
43. Song K, Cowan KH, and Sinha BK (1999). In vivo studies of adenovirusmediated p53 gene therapy for cis-platinum-resistant human ovarian tumor xenografts. Oncol Res 11, 153-159.
44. Zhang Y, Zhang Q, Zeng SX, Mayo LD, and Lu H (2012). Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth. Cancer Biol Ther 13, 915-924.
45. Chou TC and Talalay P (1984). Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22, 27-55.
46. Jafri SH, Glass J, Shi R, Zhang S, Prince M, and Kleiner-Hancock H (2010). Thymoquinone and cisplatin as a therapeutic combination in lung cancer: in vitro and in vivo. J Exp Clin Cancer Res 29, 87.
47. Carter CA, Chen C, Brink C, Vincent P, Maxuitenko YY, Gilbert KS, Waud WR, and Zhang X (2007). Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma. Cancer Chemother Pharmacol 59, 183-195.
48. Siddik ZH (2003). Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265-7279.
49. Gutekunst M, Oren M, Weilbacher A, Dengler MA, Markwardt C, Thomale J, Aulitzky WE, and van der Kuip H (2011). p53 hypersensitivity is the predominant mechanism of the unique responsiveness of testicular germ cell tumor (TGCT) cells to cisplatin. PLoS One 6, e19198.
50. Johnstone RW, Ruefli AA, and Lowe SW (2002). Apoptosis: a link between cancer genetics and chemotherapy. Cell 108, 153-164.
51. Harper JW and Elledge SJ (2007). The DNA damage response: ten years after. Mol Cell 28, 739-745.
52. Bartek J, Bartkova J, and Lukas J (2007). DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene 26, 7773-7779.
53. Zhou BB and Elledge SJ (2000). The DNA damage response: putting checkpoints in perspective. Nature 408, 433-439.
54. Jackson SP and Bartek J (2009). The DNA-damage response in human biology and disease. Nature 461, 1071-1078.
55. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, and Linn S (2004). Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73, 39-85.
56. Hurley PJ and Bunz F (2007). ATM and ATR: components of an integrated circuit. Cell Cycle 6, 414-417.
57. Cimprich KA and Cortez D (2008). ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9, 616-627.
58. Lee JH, Jin Y, He G, Zeng SX, Wang YV, Wahl GM, and Lu H (2012). Hypoxia activates tumor suppressor p53 by inducing ATR-Chk1 kinase cascademediated phosphorylation and consequent 14-3-3γ inactivation of MDMX protein. J Biol Chem 287, 20898-20903.
59. Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, and Lu H (2006). 14-3-3γ binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J 25, 1207-1218.
60. LeBron C, Chen L, Gilkes DM, and Chen J (2006). Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. EMBO J 25, 1196-1206.
61. Chen L, Gilkes DM, Pan Y, Lane WS, and Chen J (2005). ATM and Chk2-- dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. EMBO J 24, 3411-3422.
62. Iarussi D, Indolfi P, Casale F, Coppolino P, Tedesco MA, and Di Tullio MT (2001). Recent advances in the prevention of anthracycline cardiotoxicity in childhood. Curr Med Chem 8, 1649-1660.
63. Neilan TG, Blake SL, Ichinose F, Raher MJ, Buys ES, Jassal DS, Furutani E, Perez-Sanz TM, Graveline A, Janssens SP, et al. (2007). Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin. Circulation 116, 506-514.
64. Hanigan MH, Gallagher BC, Townsend DM, and Gabarra V (1999). γ-Glutamyl transpeptidase accelerates tumor growth and increases the resistance of tumors to cisplatin in vivo. Carcinogenesis 20, 553-559.
65. Hanigan MH, Lykissa ED, Townsend DM, Ou CN, Barrios R, and Lieberman MW (2001). γ-glutamyl transpeptidase-deficient mice are resistant to the nephrotoxic effects of cisplatin. Am J Pathol 159, 1889-1894.
66. Wainford RD, Weaver RJ, Stewart KN, Brown P, and Hawksworth GM (2008). Cisplatin nephrotoxicity is mediated by gamma glutamyltranspeptidase, not via a C-S lyase governed biotransformation pathway. Toxicology 249, 184-193.
67. Dhar S, Kolishetti N, Lippard SJ, and Farokhzad OC (2011). Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci USA 108, 1850-1855.
68. Lebrecht D, Geist A, Ketelsen UP, Haberstroh J, Setzer B, Kratz F, and Walker UA (2007). The 6-maleimidocaproyl hydrazone derivative of doxorubicin (DOXO-EMCH) is superior to free doxorubicin with respect to cardiotoxicity and mitochondrial damage. Int J Cancer 120, 927-934.
69. Lebrecht D, Geist A, Ketelsen UP, Haberstroh J, Setzer B, and Walker UA (2007). Dexrazoxane prevents doxorubicin-induced long-term cardiotoxicity and protects myocardial mitochondria from genetic and functional lesions in rats. Br J Pharmacol 151, 771-778.
70. Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, Cohen GI, Emami B, Gradishar WJ, Mitchell RB, et al. (2009). American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol 27, 127-145.
71. Asna N, Lewy H, Ashkenazi IE, Deutsch V, Peretz H, Inbar M, and Ron IG (2005). Time dependent protection of amifostine from renal and hematopoietic cisplatin induced toxicity. Life Sci 76, 1825-1834.
72. Kuang Y, Liu J, Liu Z, and Zhuo R (2012). Cholesterol-based anionic longcirculating cisplatin liposomes with reduced renal toxicity. Biomaterials 33, 1596-1606.
73. Rigacci L, Mappa S, Nassi L, Alterini R, Carrai V, Bernardi F, and Bosi A (2007). Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated with anthracyclines. Hematol Oncol 25, 198-203.
74. Yildirim Y, Gultekin E, Avci ME, Inal MM, Yunus S, and Tinar S (2008). Cardiac safety profile of pegylated liposomal doxorubicin reaching or exceeding lifetime cumulative doses of 550 mg/m2 in patients with recurrent ovarian and peritoneal cancer. Int J Gynecol Cancer 18, 223-227.
75. Sato S, Kigawa J, Minagawa Y, Okada M, Shimada M, Takahashi M, Kamazawa S, and Terakawa N (1999). Chemosensitivity and p53-dependent apoptosis in epithelial ovarian carcinoma. Cancer 86, 1307-1313.
76. Yang X, Fraser M, Moll UM, Basak A, and Tsang BK (2006). Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspasedependent mitochondrial death pathway. Cancer Res 66, 3126-3136.
77. Lee S, Choi EJ, Jin C, and Kim DH (2005). Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol 97, 26-34.
78. Riedel RF, Porrello A, Pontzer E, Chenette EJ, Hsu DS, Balakumaran B, Potti A, Nevins J, and Febbo PG (2008). A genomic approach to identify molecular pathways associated with chemotherapy resistance. Mol Cancer Ther 7, 3141-3149.
79. Barakat K, Gajewski M, and Tuszynski JA (2012). DNA repair inhibitors: the next major step to improve cancer therapy. Curr Top Med Chem 12, 1376-1390.
80. Pan Y, Zhang Q, Atsaves V, Yang H, and Claret FX (2012). Suppression of Jab1/CSN5 induces radio- and chemo-sensitivity in nasopharyngeal carcinoma through changes to the DNA damage and repair pathways. Oncogene, 1-11. doi: 10.1038/onc2012.294
81. Wilk A, Waligorska A, Waligorski P, Ochoa A, and Reiss K (2012). Inhibition of ERβ induces resistance to cisplatin by enhancing Rad51-mediated DNA repair in human medulloblastoma cell lines. PLoS One 7, e33867.
82. Chu G (1994). Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. J Biol Chem 269, 787-790.
83. Itoh Y, Tamai M, Yokogawa K, Nomura M, Moritani S, Suzuki H, Sugiyama Y, and Miyamoto K (2002). Involvement of multidrug resistance-associated protein 2 in in vivo cisplatin resistance of rat hepatoma AH66 cells. Anticancer Res 22, 1649-1653.
84. To KK, Yu L, Liu S, Fu J, and Cho CH (2012). Constitutive AhR activation leads to concomitant ABCG2-mediated multidrug resistance in cisplatin-resistant esophageal carcinoma cells. Mol Carcinog 51, 449-464.
85. Guntur VP, Waldrep JC, Guo JJ, Selting K, and Dhand R (2010). Increasing p53 protein sensitizes non-small cell lung cancer to paclitaxel and cisplatin in vitro. Anticancer Res 30, 3557-3564.
86. Tian B, Liu J, Liu B, Dong Y, Song Y, and Sun Z (2011). p53 Suppresses lung resistance-related protein expression through Y-box binding protein 1 in the MCF-7 breast tumor cell line. J Cell Physiol 226, 3433-3441.
87. Han JY, Lee GK, Jang DH, Lee SY, and Lee JS (2008). Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of advanced nonsmall cell lung cancer. Cancer 113, 799-807.
88. Ikuta K, Takemura K, Kihara M, Naito S, Lee E, Shimizu E, and Yamauchi A (2005). Defects in apoptotic signal transduction in cisplatin-resistant non-small cell lung cancer cells. Oncol Rep 13, 1229-1234.
89. Kandioler D, Stamatis G, Eberhardt W, Kappel S, Zochbauer-Muller S, Kuhrer I, Mittlbock M, Zwrtek R, Aigner C, Bichler C, et al. (2008). Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer. J Thorac Cardiovasc Surg 135, 1036-1041.
90. Wu ZZ and Chao CC (2010). Knockdown of NAPA using short-hairpin RNA sensitizes cancer cells to cisplatin: implications to overcome chemoresistance. Biochem Pharmacol 80, 827-837.
91. Hovelmann S, Beckers TL, and Schmidt M (2004). Molecular alterations in apoptotic pathways after PKB/Akt-mediated chemoresistance in NCI H460 cells. Br J Cancer 90, 2370-2377.
92. Wu ZZ, Sun NK, Chien KY, and Chao CC (2011). Silencing of the SNARE protein NAPA sensitizes cancer cells to cisplatin by inducing ERK1/2 signaling, synoviolin ubiquitination and p53 accumulation. Biochem Pharmacol 82, 1630-1640.
93. Lin X and Howell SB (2006). DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol Cancer Ther 5, 1239-1247.
94. Hayashi S, Ozaki T, Yoshida K, Hosoda M, Todo S, Akiyama S, and Nakagawara A (2006). p73 and MDM2 confer the resistance of epidermoid carcinoma to cisplatin by blocking p53. Biochem Biophys Res Commun 347, 60-66.
95. Bauer JA, Kumar B, Cordell KG, Prince ME, Tran HH, Wolf GT, Chepeha DB, Teknos TN, Wang S, Eisbruch A, et al. (2007). Targeting apoptosis to overcome cisplatin resistance: a translational study in head and neck cancer. Int J Radiat Oncol Biol Phys 69, S106-S108.
96. Wu ZZ, Sun NK, and Chao CC (2011). Knockdown of CITED2 using short-hairpin RNA sensitizes cancer cells to cisplatin through stabilization of p53 and enhancement of p53-dependent apoptosis. J Cell Physiol 226, 2415-2428.
97. Nadkarni A, Rajesh P, Ruch RJ, and Pittman DL (2009). Cisplatin resistance conferred by the RAD51D (E233G) genetic variant is dependent upon p53 status in human breast carcinoma cell lines. Mol Carcinog 48, 586-591.
98. Lax SA, Chia MC, Busson P, Klamut HJ, and Liu FF (2001). Adenovirus-p53 gene therapy in human nasopharyngeal carcinoma xenografts. Radiother Oncol 61, 309-312.
99. Roh JL, Ko JH, Moon SJ, Ryu CH, Choi JY, and Koch WM (2012). The p53-- reactivating small-molecule RITA enhances cisplatin-induced cytotoxicity and apoptosis in head and neck cancer. Cancer Lett 325, 35-41.
100. Li Q, Kawamura K, Yamanaka M, Okamoto S, Yang S, Yamauchi S, Fukamachi T, Kobayashi H, Tada Y, Takiguchi Y, et al. (2012). Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed. Cancer Gene Ther 19, 218-228.