Development, pharmacology, role of DT-Diaphorase and prospects of the indoloquinone EO9

General Pharmacology

Volumn 27, Issue 3, 1996, Pages 421-429

  Smitskamp Wilms, E ^a   Hendriks, H R ^b   Peters, G J ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b EORTC New Drug Development Office   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYMETHYL 5 AZIRIDINYL 1 METHYL 2 (1H INDOLE 4,7 DIONE)PROPENOL; 5 (1 AZIRIDINYL) 3 HYDROXYMETHYL 2 (3 HYDROXY 1 PROPENYL) 1 METHYL 4,7 INDOLEDIONE; ALKYLATING AGENT; INDOLOQUINOLINONE; MITOMYCIN C; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); UNCLASSIFIED DRUG;

ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; CANCER CELL CULTURE; CLINICAL TRIAL; CYTOTOXICITY; DRUG MECHANISM; ENZYME ACTIVITY; HUMAN; HYPOXIA; METABOLIC ACTIVATION; NONHUMAN; PRIORITY JOURNAL; PROTEINURIA; RADIATION; RADIOSENSITIZATION; REDUCTION; REVIEW;

EID: 0029943044     PISSN: 03063623     EISSN: None     Source Type: Journal    
DOI: 10.1016/0306-3623(95)00118-2     Document Type: Review

References (88)

1. Adams G. E., Stratford I. J., Edwards H. S., Bremner J. C. M. and Cole S. (1992) Bioreductive drugs as post-irradiation sensitizers: comparison of dual function agents with SR4233 and the Mitomycin C analogue EO9. Int. J. Radiat. Oncol. Biol. Phys. 22, 717-720.
2. Bailey S. M., Lewis A. D., Hartley J. A. and Workman P. (1994a) Involvement of DT-diaphorase in the DNA cross-linking and sequence selectivity of the novel indoloquinone antitumour agent EO9. Proc. Am. Assoc. Cancer Res. 35, 384.
3. Bailey S. M., Lewis A. D. and Workman P. (1994b) Involvement of NADPH: Cytochrome P450 reductase in activation of EO9. Br. J. Cancer 59, suppl. XXI, 57.
4. Bailey S. M., Sugget N., Walton M. I. and Workman P. (1992). Structure-activity relationships for DT-diaphorase reduction of hypoxic cell directed agents: indoloquinones and diaziridinyl benzoquinones. Int. J. Radiat. Oncol. Biol. Physics 22, 649-653.
5. Beall H. D., Mulcahy R. T., Siegel D., Traver R. D., Gibson N. W. and Ross D. (1994) Metabolism of bioreductive antitumor compounds by purified rat and human DT-diaphorases. Cancer Res. 54, 3196-3201.
6. Belinsky M. and Jaiswal A. K. (1993) NAD(P)H-Quinone oxidoreductase(1) (DT-diaphorase) expression in normal and tumor tissues. Cancer Metastasis Rev. 12, 103-117.
7. Benson A. N., Hunkeler M. J. and Talalay P. (1980) Increase of NAD(P)H: quinone reductase by dietary antioxidants: Possible role in protection against carcinogenesis and toxicity. Proc. Natl. Acad. Sci. USA 77, 5216-5220.
8. Bibby M. C., Cronin B. P. and Phillips R. (1993a) Evaluation of the cytotoxicity of the indoloquinone EO9 in a human colon adenocarcinoma model. Int. J. Oncol. 3, 661-666.
9. Bibby M. C., Sleigh N. R., Loadman P. M. and Double J. A. (1993b) Potentiation of EO9 anti-tumour activity by hydralazine. Europ. J. Cancer 29A, 1033-1035.
10. Binger M. and Workman P. (1990) Gradient high-performance liquid Chromatographic assay for the determination of the novel indoloquinone antitumour agent EO9 in biological specimens. J. Chromotog. 532, 321-336.
11. Delong M. J., Prochaska H. J. and Talalay P. (1986) Induction of NAD(P)H: quinone reductase in murine hepatoma cells by phenolic antioxidants, azo dyes, and other chemoprotectors: A model system for the study of anticarcinogens. Proc. Nad. Acad. Sci. USA 83, 787-791.
12. De Vries J. D., Winkelhorst J., Underberg W. J. M., Henrar R. E. C. and Beijnen J. H. (1993) A systematic study on the chemical stability of the novel indoloquinone antitumour agent EO9. Int. J. Pharmaceut. 100, 181-188.
13. Eickelmann P., Ebert T., Warskulat U., Schulz W. A. and Sies H. (1994) Expression of NAD(P)H:quinone oxidoreductase and glutathione S-transferases alpha and pi in human renal cell carcinoma and in kidney cancer-derived cell lines. Carcinogenesis 15, 219-225.
14. Ernster L. (1967) DT diaphorase. Methods Enzymol. 10, 309-317.
15. Ernster L. (1987) DT diaphorase: A historical review. Chemica Scripta 27A, 1-13.
16. Favreau L. V. and Pickett C. B. (1991) Transcriptional regulation of the rat NAD(P)H:quinone reductase gene-identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. J. Biol. Chem. 266, 4556-4561.
17. Fitzsimmons S. A., Workman P., Grever M., Paull K. and Lewis A. D. (1994) Differential expression of DT-diaphorase, cytochrome P450 reductase and cytochrome b5 reductase in the NCI human tumour cell lines panel. Proc. Am. Assoc. Cancer Res. 35, 369 (abstr. 2200).
18. Gasdaska P. Y., Powis G., Hyman P. and Fisher H. (1993) Cigarette smoking is a determinant of DT-diaphorase gene expression in human non-small cell lung carcinoma. Cancer Res. 53, 5458-5461.
19. Gustafson D. L. and Pritsos C. A. (1992) Bioactivation of mitomycin-C by xanthine dehydrogenase from EMT6 mouse mammary carcinoma tumors. J. Natl. Cancer Inst. 84, 1180-1185.
20. Hendriks H. R., Pizao P. E., Berger D. P., Kooistra K. L., Bibby M. C., Boven E., et al. (1993) EO9: a novel bioreductive alkylating indoloquinone with preferential solid tumour activity and lack of bone marrow toxicity in preclinical models. Europ. J. Cancer 29A, 897-906.
21. Hodnick W. F. and Sartorelli A. C. (1993) Reductive activation of mitomycin C by NADH-cytochrome b5 reductase. Cancer Res. 53, 4907-4912.
22. Jaiswal A. K. (1994). Antioxidant response element. Biochem. Pharmac. 48, 439-444.
23. Jonkman-de Vries J. D., Talsma H., Henrar R. E. C., Kettenes-van den Bosch J. J., Bull A. and Beijnen J. H. (1994) Pharmaceutical development of a patenteral lyophilized formulation of the novel indoloquinone antitumor agent EO9. Cancer Chemother. Pharmac. 34, 416-422.
24. Kal H. B. (1995) personal communication.
25. Kal H. B., Karim A. B. M. F. and Hendriks H. R. (1994) The efficacy of EO9 with radiation in experimental rat tumors. Ann. Oncol. 5, suppl. 5, 88.
26. Kappus H. (1986) Overview of enzyme systems involved in bioreduction of drugs and in redox cycling. Biochem Pharmac. 35, 1-6.
27. Kaye S. B., Workman P., Graham M. A., Cassidy J. and Jodrell D. (1993) Pharmacokinetics and early clinical studies of selected new drugs. Cancer Surveys 17, 371-396.
28. Kennedy K. A., McGurl J. D., Leondaris L. and Alabaster O. (1985) pH dependence of mitomycin C induced cross linking activity in EMT6 tumour cells. Cancer Res. 45, 3541-3547.
29. Keyes S. R., Fracasso P. M., Heimbrook D. C., Rockwell S., Sligar S. G. and Sartorelli A. C. (1984) Role of NADPH: cytochrome c reductase and DT-diaphorase in the biotransformation of mitomycin C. Cancer Res. 44, 5633-5643.
30. Lewis A. D., Holyoake T. L., Dunlop D. J., Pragnell I. D. and Workman P. (1993) Lack of myelosuppression with EO9 in human and mouse bone marrow: correlation with low DT-diaphorase. Proc. Am. Assoc. Cancer Res. 34, 345.
31. Lewis A. D., Clarke P. E., Deng P. S. K., Chen S. and Workman P. (1994) Comparison of human and rodent recombinant DT-diaphorase proteins for their ability to metabolise the novel indoloquinone antitumour agent EO9. Proc. Am. Assoc. Cancer Res. 35, 384.
32. Li Y. and Jaiswal A. K. (1992) Regulation of human NAD(P)H-quinone oxidoreductase gene-Role of AP1 binding site contained within human antioxidant response element. J. Biol. Chem. 267, 15097-15104.
33. Lind C., Cadenas E., Hochstein P. and Ernster L. (1990) DT-Diaphorase: purification, properties, and function. Methods Enzymol. 186, 287-301.
34. Lind C., Hochstein P. and Ernster L. (1982) DT-diaphorase as a quinone reductase: a cellular control device against semiquinone and Superoxide radical formation. Arch. Biochem. Biophysics. 216, 178-185.
35. Lund B., Aamdal S. and Koier I. (1994) Phase I study of the bioreductive indoloquinone EO9. Ann Oncol. 5 (suppl. 5), 136.
36. Maliepaard M., Wolfs A., Groot S. E., De Mol N. J. and Janssen H. M. (1995) Indoloquinone EO9: DNA interstrand cross-linking upon reduction by DT-diaphorase or xanthine oxidase. Br. J. Cancer, 71, 836-839.
37. Malkinson A. M., Siegel D., Forrest G. L., Gazdar A. F., Oie H. K., Chan D. C., Bunn P. A., Mabry M., Dykes D. J., Harrison S. D. and Ross D. (1992) Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma-Relationship to the response of lung tumor xenografts to mitomycin-C. Cancer Res. 52, 4752-4757.
38. Martius C. (1963) Quinone reductases. The Enzymes part 7, 517-531.
39. Oostveen E. A. and Speckamp W. N. (1987) Mitomycin analogues 1. Indoloquinones as potent bisalkylating agents. Tetrahedron 43, 255-262.
40. Pan S., Andrews P. A., Glover C. J. and Bachur N. R. (1984) Reductive activation of mitomycin C and mitomycin C metabolites by N ADPH-cytochrome P-450 reductase and xanthine oxidase. J. Biol. Chem. 259, 959-966.
41. Paull K., Camalier R. Fitzsimmons S. A., Lewis A. D., Workman P. and Grever M. (1994) Correlations of DT-diaphorase expression with cell sensitivity data obtained from the NCI human tumor cell line panel. Proc. Am. Ass. Cancer Res. 35, 369.
42. Paull K. D., Shoemaker R. H., Hodes L. et al. (1989). Display and analysis of patterns of differential activity of drugs against human tumor cell lines: Development of mean graph and COMPARE Algorithm. J. Natl. Cancer Inst. 81, 1088-1092.
43. Phillips R. M., Bibby M. C. and Double J. A. (1988) Experimental correlations of in vitro drug sensitivity with in vivo response to thioTEPA in a panel of murine colon tumours. Cancer Chemother. Pharmac. 21, 168-172.
44. Phillips R. M., De la Cruz A., Traver R. D. and Gibson N. W. (1994) Increased activity and expression of NAD(P)H:Quinone acceptor oxidoreductase in confluent cell cultures and within multicellular spheroids. Cancer Res. 54, 3766-3771.
45. Phillips R. M., Hulbert P. B., Bibby M. C., Sleigh N. R. and Double J. A. (1992) In vitro activity of the novel indoloquinone EO-9 and the influence of pH on cytotoxicity. Br. J. Cancer. 65, 359-364.
46. Pizao P. E., Peters G. J., Van Ark-Otte J., Smets L. A., Smitskamp-Wilms E., Winograd B., Pinedo H. M. and Giaccone G. (1993) Cytotoxic effects of standard and investigational anticancer agents on subconfluent and multilayered postconfluent cultures growing in "V" bottomed microtiter plates. Europ. J. Cancer 29A, 1566-1573.
47. Plumb J. A., Gerritsen M., Milroy R., Thomson P. and Workman P. (1994a) Relative importance of DT-diaphorase and hypoxia in the bioactivation of EO9 by human lung tumor cell lines. Int. J. Radiat. Oncol. Biol. Phys. 29, 295-299.
48. Plumb J. A. and Workman P. (1994) Unusually marked hypoxic sensitization to indoloquinone EO9 and mitomycin C in a human colon-tumour cell line that lacks DT-diaphorase activity. Int. J. Cancer 56, 134-139.
49. Plumb J. A., Gerritsen M. and Workman P. (1994b). DT-diaphorase protects cells from the hypoxic toxicity of indoloquinone EO9. Br. J. Cancer 70, 1136-1143.
50. Pritsos C. A. and Sartorelli A. C. (1986) Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics. Cancer Res. 46, 3528-3532.
51. Prochaska H.J. and Talalay P. (1988) Regulatory mechanisms of monofunctional and bifunctional anticarcinogenic enzyme inducers in murine livers. Cancer Res. 48, 4776-4782.
52. Quinn P. K. M., Bibby M. C., Crawford S. M. and Cox J. A. (1991) Hydralazine affects the blood flow through a series of experimental colon tumours. Int. J. Radiat. Biol. 60, 224.
53. Rauth A. M., Marshall R. S. and Kuehl B. L. (1993) Cellular approaches to bioreductive drug mechanisms. Cancer Metastasis Rev. 12, 153-164.
54. Riley R. J. and Workman P. (1992) DT-diaphorase and cancer chemotherapy. Biochem. Pharmac. 43, 1657-1669.
55. Robertson N., Stratford 1. J., Houlbrook S., Carmichael J. and Adams G. E. (1992) The sensitivity of human tumour cells to quinone bioreductive drugs: What role for DT-diaphorase? Biochem. Pharmac. 44, 409-412.
56. Robertson N., Haigh A., Adams G. E. and Stratford I. J. (1994) Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia. Eur. J. Cancer 30a, 1013-1019.
57. Rockwell S., Sartorelli A. C., Tomasz M. and Kennedy K. A. (1993) Cellular pharmacology of quinone bioreductive alkylating agents. Cancer Metastasis Rev. 12, 165-176.
58. Roed H., Aabo K., Vindelov L., Spang-Thomsen M., Christensen I. J. and Hansen H. H. (1989) In vitro and in vivo evaluation of the indoloquinone EO-9 (NSC 382 459) against small cell carcinoma of the lung. Europ. J. Cancer Clin. Oncol. 25, 1197-1201.
59. Ross D., Siegel D., Gibson N. W., Pacheco D., Thomas D. J., Reasor M. and Wierda D. (1990) Activation and deactivation of quinones catalyzed by DT-diaphorase. Evidence for bioreductive activation of diaziquone (AZQ) in human tumor cells and detoxification of benzene metabolites in bone marrow stroma. Free Rad. Res. Comms. 8, 373-381.
60. Ross D., Siegel D., Beall H., Prakash A. S., Mulcahy R. T. and Gibson N. W. (1993) DT-diaphorase in activation and detoxification of quinones-bioreductive activation of mitomycin-C. Cancer Metastasis Rev. 12, 83-101.
61. Sartorelli A. C. (1986) The role of mitomycin antibiotics in the chemotherapy of solid tumors. Biochem Pharmac. 35, 67-69.
62. Schellens J. H. M., Planting A. S. T., Van Acker B. A. C., Loos W. J., De Boer-Dennert M., Van der Burg M. E. L., Koier I., Krediet R. T., Stoter G. and Verweij J. (1994) Phase 1 and pharmacologic study of the novel indoloquinone bioreductive alkylating cytotoxic drug EO9. J. Natl. Cancer Inst. 86, 906-912.
63. Schlager J. J., Hoerl B. J., Riebow J., Scott D. P., Gasdaska P., Scott R. E. and Powis G. (1993). Increased NAD(P)D: (quinone-acceptor)oxidoreducase activity is associated with density-dependent growth inhibition of normal but not transformed cells. Cancer Res. 53, 1338-1342.
64. Schlager J. J. and Powis G. (1990) Cytosolic NAD(P)D:(quinone-acceptor)oxidoreducase in human normal and tumor tissue: effects of cigarette smoking and alcohol. Int. J. Cancer. 45, 403-409.
65. Siegel D., Beall H., Senekowitsch C., Kasai M., Arai H., Gibson N. W. and Ross D. (1992) Bioreductive activation of mitomycin-C by DT-diaphorase. Biochemistry 31, 7879-7885.
66. Siegel D., Gibson N. W., Preusch P. C. and Ross D. (1990a) Metabolism of diaziquone by NAD(P)H:(quinone acceptor) oxidoreductase: role in diaziquone-induced DNA damage and cytotoxicity in human colon carcinoma cells. Cancer Res. 50, 7293-7300.
67. Siegel D., Gibson N. W., Preusch P. C. and Ross D. (1990b) Metabolism of mitomycin C by DT-diaphorase: role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells. Cancer Res. 50, 7483-7489.
68. Smitskamp-Wilms E., PetersG. J., Pinedo H. M., Van Ark-Otte J. and Giaccone G. (1994) Chemosensitivity to the indoloquinone EO9 is correlated with DT-diaphorase activity and its gene expression. Biochem. Pharmac. 47, 1325-1332.
69. Smitskamp-Wilms E., Giaccone G., Pinedo H. M., Vanderlaan B. F. A. M. and Peters G. J. (1995) DT-diaphorase activity in normal and neoplastic human tissues; an indicator for sensitivity to bioreductive agents? Br. J Cancer, 72, 917-921.
70. Speckamp W. N. and Oostveen E. A. (1986) The indoloquinones. Br. Pat. Appl. no 86.09369.
71. Tomasz M., Lipman R., Chowdary D., Pawlak J., Verdine G. L. and Nakanishi K. (1987) Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA. Science 235, 1204-1208.
72. Traver R. D., Horikoshi T., Danenberg K. D., Stadibauer T. H. W., Danenberg P. V., Ross D. and Gibson N. W. (1992) NAD(P)H-quinone oxidoreductase gene expression in human colon carcinoma cells-characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. Cancer Res. 52, 797-802.
73. Van Ark-Otte J., Peters G. J., Pizao P. E., Keepers Y. P. A. M. and Giaccone G. (1994) In vitro schedule-dependence of EO9 and miltefosine in comparison to standard drugs in colon cancer cells. Int. J. Oncol. 4, 709-715.
74. Verwey J., Den Hartigh J., Stuurman M., De Vries J. and Pinedo H. M. (1987) Relationship between clinical parameters and pharmacokinetics of mitomycin C. J. Cancer Res. Clin. Oncol. 113, 91-94.
75. Wallin R., Gebhardt O. and Prydz H. (1978) NAD(P)H dehydrogenase and its role in vitamin K (2-methyl-3-phytyl-1,4-naphtaquinone)-dependent carbox-ylation reaction. Biochem. J. 169, 95-101.
76. Walton M. I., Smith P. J. and Workman P. (1991) The role of NAD(P)H:quinone reductase (EC 1.6.99.2, DT-diaphorase) in the reductive bioactivation of the novel indoloquinone antitumor agent EO9. Cancer Communic. 3, 199-206.
77. Walton M.I., Sugget N. and Workman P. (1992a) The role of human and rodent DT-diaphorase in the reductive metabolism of hypoxic cell cytotoxins. Int. J. Radiat. Oncol Biol. Phys. 22, 643-647.
78. Walton M. I., Bibby M. C., Double J. A., Plumb J. A. and Workman P. (1992b) DT-diaphorase activity correlates with sensitivity to the indoloquinone-EO9 in mouse and human colon carcinomas. Europ. J. Cancer 28A, 1597-1600.
79. Wanders J., Pavlidis N., Gamucci T., Ten Bohhel Huinink W. W., Dirix L., Wolff I. and Verwey J. (1995) Phase II studies with EOg in breast, colorectal, gastric, pancreatic and NSCLC. Europ. J. Cancer 31A, Suppl. 5, S120 (no. 565).
80. Wermuth B. (1981) Purification and properties of an NADPH dependent carbonyl reductase from human brain. J. Biol. Chem. 256, 1206-1213.
81. Winograd B., Lobbezoo M. W., Double J., Fiebig H. H., Lelieveld P., Workman P. and Pinedo H. M. (1989) Preclinical antitumor profile of EO9, a novel bioreductive alkylating indoloquinone derivative. Proc. Am. Assoc. Cancer Res. 30, 582.
82. Workman P. (1992) Keynote Adress: Bioreductive mechanisms. Int. J. Radiat. Oncol. Biol. Phys. 22, 631-637.
83. Workman P., Binger M. and Kooistra K. (1992) Pharmacokinetics, distribution and metabolism of the novel bioreductive alkylating indoloquinone EO9 in rodents. Int. J. Radiat. Oncol. Biol. Phys. 22, 713-716.
84. Workman P. and Stratford I. J. (1993) The experimental development of bioreductive drugs and their role in cancer therapy. Cancer Metastasis Rev. 12, 73-82.
85. Workman P., Walton M. I., Powis G. and Schlager J. J. (1989) DT-diaphorase: questionable role in mitomycin C resistance, but a target for novel bioreductive drugs? Br. J. Cancer 60, 800-802.
86. Workman P. and Walton M. I. (1990) Enzyme directed bioreductive drug development. In Selective activation of drugs by redox processes. (Edited by Adams G. E., Breccia A., Fielden E. M., Wardman P.) pp. 173-191. Plenum Press: New York.
87. Workman P., Walton M. I., Bibby M. C. and Double J. A. (1990) In vivo response of mouse adenocarcinoma of the colon (MAC) tumours to indoloquinone EO9: correlation with bioreductive enzyme content. Br. J. Cancer 62, 515-516.
88. Yao K. S., Clayton M. and O'Dwyer P. J. (1994) Interaction of heat and hypoxia in modulating transcription of DT diaphorase in human colon adenocarcinoma cells. Cell Growth Differentiation. 5, 125-131.