ArticleBritish journal of cancer1997
Overexpression of human NADPH:cytochrome c (P450) reductase confers enhanced sensitivity to both tirapazamine (SR 4233) and RSU 1069.
Article in British journal of cancer, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 94 citations in OpenAlex.
- An oxygen gradient chamber with simple geometry for generating oxygen gradients in hydrogel-based cell cultures within a well-plate-compatible format.Frontiers in bioengineering and biotechnology · 2026Article
- Versatile Stimuli-Responsive Controlled Release of Pinanediol-Caged Boronic Esters for Spatiotemporal and Nitroreductase-Selective Glucose Bioimaging.ACS sensors · 2025Article
- Redox Proteomic Profile of Tirapazamine-Resistant Murine Hepatoma Cells.International journal of molecular sciences · 2023Article
- Review
- Flavylium-Based Hypoxia-Responsive Probe for Cancer Cell Imaging.Molecules (Basel, Switzerland) · 2021Article
- Subcellular Location of Tirapazamine Reduction Dramatically Affects Aerobic but Not Anoxic Cytotoxicity.Molecules (Basel, Switzerland) · 2020Article
- Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials.Clinical and translational radiation oncology · 2019Article
- Hypoxia-activated prodrugs: paths forward in the era of personalised medicine.British journal of cancer · 2016Review
- Quinoxaline 1,4-di-N-Oxides: Biological Activities and Mechanisms of Actions.Frontiers in pharmacology · 2016Review
- Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia.Chinese journal of cancer · 2014Review
- Zinc finger nuclease knock-out of NADPH:cytochrome P450 oxidoreductase (POR) in human tumor cell lines demonstrates that hypoxia-activated prodrugs differ in POR dependence.The Journal of biological chemistry · 2013Article
- The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines.British journal of cancer · 2005Article
- Oxygen-sensitive enzyme-prodrug gene therapy for the eradication of radiation-resistant solid tumours.Gene therapy · 2002Article
- Hypoxia and oxidative stress. Tumour hypoxia--therapeutic considerations.Breast cancer research : BCR · 2001Review
- NADPH:cytochrome c (P450) reductase activates tirapazamine (SR4233) to restore hypoxic and oxic cytotoxicity in an aerobic resistant derivative of the A549 lung cancer cell line.British journal of cancer · 2000Article
- Does reductive metabolism predict response to tirapazamine (SR 4233) in human non-small-cell lung cancer cell lines?British journal of cancer · 1999Article
- Molecular chemotherapy for breast cancer.Drugs & aging · 1999Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
P450 reductase (NADPH: cytochrome c (P450) reductase, EC 1.6.2.4) plays an important role in the reductive activation of the bioreductive drug tirapazamine (SR4233). Thus, in a panel of human breast cancer cell lines, expression of P450 reductase correlated with both the hypoxic toxicity and the metabolism of tirapazamine [Patterson et al (1995) Br J Cancer 72: 1144-1150]. To examine this dependence in more detail, the MDA231 cell line, which has the lowest activity of P450 reductase in our breast cell line panel, was transfected with the human P450 reductase cDNA. Isolated clones expressed a 78-kDa protein, which was detected with anti-P450 reductase antibody, and were shown to have up to a 53-fold increase in activity of the enzyme. Using six stable transfected clones covering the 53-fold range of activity of P450 reductase, it was shown that the enzyme activity correlated directly with both hypoxic and aerobic toxicity of tirapazamine, and metabolism of the drug under hypoxic conditions. No metabolism was detected under aerobic conditions. For RSU1069, toxicity was also correlated with P450 reductase activity, but only under hypoxic conditions. Measurable activity of P450 reductase was found in a selection of 14 primary human breast tumours. Activity covered an 18-fold range, which was generally higher than that seen in cell lines but within the range of activity measured in the transfected clones. These results suggest that if breast tumours have significant areas of low oxygen tension, then they are likely to be highly sensitive to the cytotoxic action of tirapazamine and RSU 1069.
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