ArticleCancer gene therapy2006
Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N.
Article in Cancer gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 40 citations in OpenAlex.
- Cytochrome P450 Binding and Bioactivation of Tumor-Targeted Duocarmycin Agents.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer.Scientific reports · 2021Article
- Extrahepatic cytochrome P450 epoxygenases: pathophysiology and clinical significance in human gastrointestinal cancers.Oncotarget · 2021Review
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 2021Review
- Structures of human cytochrome P450 1A1 with bergamottin and erlotinib reveal active-site modifications for binding of diverse ligands.The Journal of biological chemistry · 2018Article
- A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Article
- Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia.Chinese journal of cancer · 2014Review
- Cytochrome P450-activated prodrugs.Future medicinal chemistry · 2013Review
- Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment.OncoTargets and therapy · 2013Article
- Efficient hypoxic activation of the anticancer agent AQ4N by CYP2S1 and CYP2W1.Molecular pharmacology · 2010Article
- Reductive heme-dependent activation of the n-oxide prodrug AQ4N by nitric oxide synthase.Journal of medicinal chemistry · 2008Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug metabolizing transgene products, which activate bioreductive cytotoxins, can be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6 transgenes with AQ4N and radiation inhibits tumor growth. Here we examine the ability of other CYPs, in particular CYP1A1, to metabolize AQ4N, and to enhance radiosensitization. Metabolism of AQ4N was assessed using microsomes prepared from baculovirus-infected cells transfected with various CYP isoforms. AQ4N metabolism was most efficient with CYP1A1 (66.7 nmol/min/pmol) and 2B6 (34.4 nmol/min/pmol). Transient transfection of human CYP1A1+/-CYP reductase (CYPRED) was investigated in hypoxic RIF-1 mouse cells in vitro using the alkaline comet assay. There was a significant increase in DNA damage following transient transfection of CYP1A1 compared to non-transfected cells; inclusion of CYPRED provided no additional effect. In vivo, a single intra-tumoral injection of a CYP1A1 construct in combination with AQ4N (100 mg/kg i.p.) and 20 Gy X-rays caused a 16-day delay in tumor regrowth compared to tumors receiving AQ4N plus radiation and empty vector (P=0.0344). The results show the efficacy of a CYP1A1-mediated GDEPT strategy for bioreduction of AQ4N.
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