Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage

Carcinogenesis

Volumn 35, Issue 3, 2014, Pages 692-702

  Paranjpe, Ameya ^a   Zhang, Ruiwen ^a   Ali Osman, Francis ^b   Bobustuc, George C ^c   Srivenugopal, Kalkunte S ^a  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Neuro Oncology Section Aurora Advanced Cancer Care   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 O BENZYLGUANINE; ALKYLATING AGENT; CARMUSTINE; COPPER CHLORIDE; CYSTEINE DERIVATIVE; DISULFIRAM; DNA; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; PROTEASOME; TEMOZOLOMIDE; UBIQUITIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BRAIN LEVEL; CELL KILLING; CELL SURVIVAL; CONTROLLED STUDY; CYTOTOXICITY; DNA ALKYLATION; DNA CROSS LINKING; DNA DAMAGE; DNA REPAIR; DOSE RESPONSE; DRUG POTENTIATION; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME INHIBITION; ENZYME MODIFICATION; ENZYME REPRESSION; FEMALE; G2 PHASE CELL CYCLE CHECKPOINT; GLIOBLASTOMA; GLIOMA CELL; HUMAN; HUMAN CELL; LIVER LEVEL; MALE; MEDULLOBLASTOMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; TUMOR CELL LINE; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; BRAIN; BRAIN NEOPLASMS; CELL LINE, TUMOR; DISULFIRAM; DNA DAMAGE; ENZYME INHIBITORS; HUMANS; MICE; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE;

EID: 84895819755     PISSN: 01433334     EISSN: 14602180     Source Type: Journal    
DOI: 10.1093/carcin/bgt366     Document Type: Article

References (68)

1. 6-alkylguanine by alkyltransferases. Mutat. Res., 462, 83-100.
2. Mishina,Y. et al. (2006) Direct reversal of DNA alkylation damage. Chem. Rev., 106, 215-232.
3. 6-methylguanine. Mutagenesis, 17, 483-487.
4. 6-benzylguanine or 1,3-bis(2-chloroethyl)- 1-nitrosourea. Biochemistry, 35, 1328-1334.
5. 6-methylguanine -DNA methyltransferase levels in tissues of methionine-cysteine deficient subadult and adult mice. Comp. Biochem. Physiol., 91C, 603-606.
6. Rydberg,B. et al. (1982) Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction. EMBO J., 1, 211-216.
7. Belinsky,S.A. et al. (1982) Effect of chronic ethanol diet on the replication, alkylation, and repair of DNA from hepatocytes and nonparenchymal cells following dimethylnitrosamine administration. Carcinogenesis, 3, 1293-1297.
8. 6-methylguanine DNA lesions in castrated adult male rats. Alcohol Clin. Exp. Res., 18, 1267-1271.
9. 6-methylguanine transferase. Carcinogenesis, 9, 761-766.
10. 6-methylguanine DNA methyltransferase in chronic liver diseases. Alcohol Clin. Exp. Res., 20, 297A-300A.
11. Jørgensen,C.H. et al. (2011) The efficacy of disulfiram for the treatment of alcohol use disorder. Alcohol Clin. Exp. Res., 35, 1749-1758.
12. Gaval-Cruz,M. et al. (2009) Mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol. Interv., 9, 175-187.
13. Lipsky,J.J. et al. (2001) In vivo inhibition of aldehyde dehydrogenase by disulfiram. Chem. Biol. Interact., 130-132, 93-102.
14. Viquez,O.M., et al. (2012) Electrophilic adduction of ubiquitin activating enzyme E1 by N,N-diethyldithiocarbamate inhibits ubiquitin activation and is accompanied by striatal injury in the rat. Chem. Res. Toxicol., 25, 2310-2321.
15. Paranjpe,A. et al. (2013) Degradation of NF-κB, p53 and other regulatory redox-sensitive proteins by thiol-conjugating and -nitrosylating drugs in human tumor cells. Carcinogenesis, 34, 990-1000.
16. Gerson,S.L. (2002) Clinical relevance of MGMT in the treatment of cancer. J. Clin. Oncol., 20, 2388-2399.
17. 6-methylguanine-DNA methyltransferase with specific inhibitors as a strategy in cancer therapy. Cell. Mol. Life Sci., 67, 3663-3681.
18. 6-alkylguanine DNA alkyltransferase as a means to enhance chemotherapy. Cancer Treat. Rev., 32, 261-276.
19. Kreklau,E.L. et al. (1999) Prolonged inhibition of O(6)-methylguanine DNA methyltransferase in human tumor cells by O(6)-benzylguanine in vitro and in vivo. J. Pharmacol. Exp. Ther., 291, 1269-1275.
20. 6-benzylguanine and 1,3-bis(2-chloroethyl)-nitrosourea or temozolomide. Hum. Gene Ther., 15, 758-769.
21. 6-alkylguanine-DNA alkyltransferase: low pKa and high reactivity of cysteine 145. Biochemistry, 42, 10965-10970.
22. Niture,S.K. et al. (2005) Human MGMT is a prime target for inactivation by oxidative stress, mediated by glutathionylation and oxidation of the active site cysteine145. Proc. Am. Assoc. Cancer Res., 46, 857.
23. Liu,L. et al. (2002) Inactivation and degradation of O(6)-alkylguanine- DNA alkyltransferase after reaction with nitric oxide. Cancer Res., 62, 3037-3043.
24. Cen,D. et al. (2004) Disulfiram facilitates intracellular Cu uptake and induces apoptosis in human melanoma cells. J. Med. Chem., 47, 6914-6920.
25. 6-alkylguanine-DNA alkyltransferase in human brain tumor cells. Cancer Res., 60, 282-287.
26. 6-methylguanine-DNA methyltransferase activity and its application to human neoplastic and nonneoplastic tissues. Carcinogenesis, 5, 1061-1064.
27. Ali-Osman,F. et al. (1995) Formation and repair of 1,3-bis-(2-chloroethyl)- 1-nitrosourea and cisplatin induced total genomic DNA interstrand crosslinks in human glioma cells. Cancer Biochem. Biophys., 14, 231-241.
28. Vega-Avila,E. et al. (2011) An overview of colorimetric assay methods used to assess survival or proliferation of mammalian Cells. Proc. West. Pharmacol. Soc., 54, 10-14.
29. Niture,S.K. et al. (2005) S-thiolation mimicry: quantitative and kinetic analysis of redox status of protein cysteines by glutathione-affinity chromatography. Arch. Biochem. Biophys., 444, 174-184.
30. Georgiadis,P. et al. (2012) Progress in high-throughput assays of MGMT and APE1 activities in cell extracts. Mutat. Res., 736, 25-32.
31. 6-methylguanine-DNA methyltransferase. Biochemistry, 36, 5769-5776.
32. Hough,R. et al. (1984) Effects of temperature on the degradation of proteins in rabbit reticulocyte lysates and after injection into HeLa cells. Proc. Natl. Acad. Sci. USA, 81, 90-94.
33. 6-benzylguanine is associated with prolonged G2/M arrest in cancer cells treated with BCNU. Oncogene, 24, 2175-2183.
34. Guo,X. et al. (2010) Disulfiram/copper complex inhibiting NFkappaB activity and potentiating cytotoxic effect of gemcitabine on colon and breast cancer cell lines. Cancer Lett., 290, 104-113.
35. Rothbarth,J. et al. (2004) Immunohistochemical detection of melphalan- DNA adducts in colon cancer cells in vitro and human colorectal liver tumours in vivo. Biochem. Pharmacol., 67, 1771-1778.
36. 6-methylguanine- DNA methyltransferase by dexamethasone in glioblastomas. J. Neurosurg., 101, 659-663.
37. Cvek,B. (2011) Antabuse repurposing: We need more knowledge and wide international support. Int. J. Cancer, 129, 1286-1287.
38. Brar,S.S. et al. (2004) Disulfiram inhibits activating transcription factor/ cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol. Cancer Ther., 3, 1049-1060.
39. Loo,T.W. et al. (2004) Disulfiram metabolites permanently inactivate the human multidrug resistance P-glycoprotein. Mol. Pharm., 1, 426-433.
40. Cvek,B. (2011) Targeting malignancies with disulfiram (Antabuse): multidrug resistance, angiogenesis, and proteasome. Curr. Cancer Drug Targets, 11, 332-337.
41. Liu,P. et al. (2012) Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br. J. Cancer, 107, 1488-1497.
42. Triscott,J. et al. (2012) Disulfiram, a drug widely used to control alcoholism, suppresses the self-renewal of glioblastoma and overrides resistance to temozolomide. Oncotarget, 3, 1112-1123.
43. Gunasekaran,S. et al. (1983) Distribution of disulfiram in brain after carotid ligation in gerbils. Neuropharmacology, 22, 1159-1163.
44. Bhadhprasit,W. et al. (2012) Effect of copper and disulfiram combination therapy on the macular mouse, a model of Menkes disease. J. Trace Elem. Med. Biol., 26, 105-108.
45. Kim,Y.J., et al. (2011) S-glutathionylation of cysteine 99 in the APE1 protein impairs abasic endonuclease activity. J. Mol. Biol., 414, 313-326.
46. Montaudon,D. et al. (2007) Inhibition of topoisomerase I cleavage activity by thiol-reactive compounds: importance of vicinal cysteines 504 and 505.J. Biol. Chem., 282, 14403-14412.
47. DeAngelis,L.M. (2001) Brain tumors. N. Engl. J. Med., 344, 114-123.
48. Merchant,T.E. et al. (2010) Brain tumors across the age spectrum: biology, therapy and late effects. Semin. Radiat. Oncol., 20, 58-66.
49. Grondin,R.T. et al. (2009) Pediatric brain tumors. Adv. Pediatr., 56, 249-269.
50. Neyns,B. et al. (2010) The role of cytotoxic drugs in the treatment of central nervous system gliomas. Acta Neurol. Belg., 110, 1-14.
51. Kil,W.J. et al. (2008) In vitro and in vivo radiosensitization induced by the DNA methylating agent temozolomide. Clin. Cancer Res., 14, 931-938.
52. Kast,R.E. et al. (2013) A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care. Oncotarget, 4, 502-530.
53. ClinicalTrials.gov. Phase I Study of Disulfiram and Copper Gluconate for the Treatment of Refractory Solid Tumors Involving the Liver. http://clinicaltrials.ct2/show/NCT00742911. (21 July 2013, date last accessed).
54. Johansson,B. (1992) A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites. Acta Psychiatr. Scand. Suppl., 369, 15-26.
55. Kreklau,E.L. et al. (2001) Comparison of single- versus double-bolus treatments of O(6)-benzylguanine for depletion of O(6)-methylguanine DNA methyltransferase (MGMT) activity in vivo: development of a novel fluorometric oligonucleotide assay for measurement of MGMT activity. J. Pharmacol. Exp. Ther., 297, 524-530.
56. Liu,L. et al. (2001) Differential degradation rates of inactivated alkyltransferase in blood mononuclear cells and tumors of patients after treatment with O(6)-benzylguanine. Clin. Cancer Res., 7, 2318-2324.
57. Friedman,H. et al. (1992) Enhancement of nitrosourea activity in medulloblastoma and glioblastoma multiforme. J. Natl. Cancer Inst., 84, 1926-1931.
58. Belanisch,M. et al. (1996) Retrospective study of the correlation between DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res., 56, 783-788.
59. 6-methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J. Clin. Oncol., 16, 3310-3315.
60. Martin,B. et al. (2004) Disulfiram therapy in patients with hepatitis C: a 12-month, controlled, follow-up study. J. Stud. Alcohol, 65, 651-657.
61. Wickström,M. et al. (2007) Pharmacological profiling of disulfiram using human tumor cell lines and human tumor cells from patients. Biochem. Pharmacol., 73, 25-33.
62. Shian,S.G. et al. (2003) Inhibition of invasion and angiogenesis by zincchelating agent disulfiram. Mol. Pharmacol., 64, 1076-1084.
63. Hothi,P. et al. (2012) High-throughput chemical screens identify disulfiram as an inhibitor of human glioblastoma stem cells. Oncotarget, 3, 1124-1136.
64. Vasiliou,V. et al. (2000) Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism. Chem. Biol. Interact., 129, 1-19.
65. Logan,B.K. et al. (2000) Endogenous ethanol 'auto-brewery syndrome' as a drunk-driving defense challenge. Med. Sci. Law. 40, 206-215.
66. Schafer,A. et al. (2012) Aldehyde dehydrogenase 1A1-a new mediator of resistance to temozolomide in glioblastoma. Neuro Oncol., 14, 1452-1464.
67. 6-methylguanine-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma. Int. J. Mol. Med., 11, 65-69.
68. 6-methylguanine-DNA methyltransferase: promoter hypermethylation associated with decreased expression and G:C to A:T mutations of p53 in brain tumors. Mol. Carcinog., 36, 23-31.