The relative importance of NADPH: Cytochrome c (P450) reductase for determining the sensitivity of human tumour cells to the indolequinone EO9 and related analogues lacking functionality at the C-2 and C-3 positions

Biochemical Pharmacology

Volumn 59, Issue 8, 2000, Pages 993-996

  Saunders, Mark P ^a   Jaffar, Mohammed ^a   Patterson, Adam V ^a   Nolan, John ^b   Naylor, Matthew A ^b   Phillips, Roger M ^c   Harris, Adrian L ^d   Stratford, Ian J ^a  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b MOUNT VERNON HOSPITAL   (United Kingdom)

^c UNIVERSITY OF BRADFORD   (United Kingdom)

^d JOHN RADCLIFFE HOSPITAL   (United Kingdom)

Author keywords

Cytochrome P450 reductase; EO9; Indolequinone bioreductive drugs; Transfected P450R

Indexed keywords

5 (1 AZIRIDINYL) 3 HYDROXYMETHYL 2 (3 HYDROXY 1 PROPENYL) 1 METHYL 4,7 INDOLEDIONE; QUINONE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE FERRIHEMOPROTEIN REDUCTASE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CONTROLLED STUDY; DRUG ACTIVATION; HUMAN; HUMAN CELL; PREDICTION; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; AZIRIDINES; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INDOLEQUINONES; INDOLES; NADPH-FERRIHEMOPROTEIN REDUCTASE; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 0033961216     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(99)00405-0     Document Type: Article

References (16)

1. Höckel M., Schlenger K., Mitze M., Schaffer U., Vaupel P. Hypoxia and radiation response in human tumors. Seminars Rad Oncol. 6:1996;3-9.
2. Teicher B.A. Hypoxia and drug resistance. Cancer Metastasis Rev. 13:1994;139-168.
3. Naylor M.A., Jaffar M., Nolan J., Stephens M.A., Butler S., Patel K.B., Everett S.A., Adams G.E., Stratford I.J. 2-Cyclopropylindolequinones and their analogues as bioreductively activated antitumour agents Structure-activity in vitro and efficacy in vivo . J Med Chem. 30:1997;2335-2346.
4. Speckamp WN and Oostveen EN, Indolequinone compounds. Int. Patent WO 87/06227, 1987.
5. Franck R.W., Tomasz M. The chemistry of mitomycins. Wilman D.E. Chemistry of Antitumour Agents. 1990;379-393 Blackie and Son, Glasgow.
6. Oostveen E.A., Speckamp W.N. Mitomycin analogues I. Indolequinones as (potential) bisalkylating agents. Tetrahedron. 43:1987;255-262.
7. Cotterill A.S., Moody C.J., Mortimer R.J., Norton C.L., O'Sullivan N., Stephens M.A., Stradiotto N.R., Swann E., Stratford I.J. Cyclopropamitosenes, novel bioreductive anticancer agents. Synthesis, electrochemistry, and biological activity of 7-substituted cyclopropylmitosenes and related compounds. J Med Chem. 37:1994;3834-3847.
8. Bailey S.M., Sugget N., Walton M.I., Workman P. Structure-activity relationships for DT-diaphorase reduction of hypoxic cell directed agents Indolequinones and aziridinyl benzoquinones . Int J Radiat Oncol Biol Phys. 22:1992;649-653.
9. Robertson N., Stratford I.J., Houlbrook S., Carmichael J., Adams G.E. The sensitivity of human tumour cells to quinone bioreductive drugs What role for DT-diaphorase . Biochem Pharmacol. 33:1992;409-412.
10. Phillips R.M. Bioreductive activation of a series of analogues of 5-aziridinyl-3-hydroxymethyl-1-methyl-2-[1H-indole-4,7-dione]prop-β-en- α-ol (EO9) by human DT-diaphorase. Biochem Pharmacol. 52:1996;1711-1718.
11. Bailey S.M., Lewis A.D., Hartley J.A., Workman P. Involvement of DT-diaphorase in the DNA cross-linking and sequence selectivity of the novel indolequinone antitumour agent EO9. Proc Am Assoc Cancer Res. 25:1994;384.
12. Jaffar M., Naylor M.A., Robertson N., Lockyer S.D., Phillips R.M., Everett S.A., Adams G.E., Stratford I.J. 5-Substituted analogues of 3-hydroxymethyl-5-aziridinyl-1-methyl-2-[1H-indole-4,7-dione]prop-2-en-1-ol (EO9, NSC 382459) and their regioisomers as hypoxia-selective agents Structure-cytotoxicity in vitro . Anticancer Drug Des. 12:1998;105-123.
13. Jaffar M., Naylor M.A., Robertson N., Stratford I.J. Targeting hypoxia with a new generation of indolequinones. Anticancer Drug Des. 13:1998;593-609.
14. Bailey S.M., Lewis A.D., Workman P. Involvement of NADPH cytochrome P450 reductase in activation of EO9 to a DNA damage species . Br J Cancer. 69:1994;57.
15. Robertson N., Haigh A., Adams G.E., Stratford I.J. Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro DT-diaphorase activity and hypoxia . Eur J Cancer. 30A:1994;1013-1019.
16. Patterson A.V., Saunders M.P., Chinje E.C., Talbot D.C., Harris A.L., Stratford I.J. Overexpression of human NADPH cytochrome c (P450) reductase confers enhanced sensitivity to both tirapazamine (SR4233) and RSU 1069 . Br J Cancer. 76:1997;1338-1347.