Browse by author
Lookup NU author(s): Dr David Jamieson, Kerrie Wilson, Dr Simon Pridgeon, Dr Jane Margetts, Professor Richard Edmondson, Professor Hing Leung, Professor Alan Boddy
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Purpose: NRH:quinone oxidoreductase 2 (NQO2) is a homologue of NAD(P)H:quinone oxidoreductase 1 (NQO1). Despite 54% homology with human NQO1, NQO2 has little endogenous enzymatic activity. However, NQO2 has potential as a therapeutic target because the addition of the nonbiogenic electron donor dihydronicotinamide riboside (NRH) selectively potentiates the bioactivation of the alkylating agent tretazicar (CB 1954). The NQO activity of ovarian and bladder tumors was determined and the effect of NQO polymorphisms on NQO activity was investigated. Experimental Design: Intraperitoneal ovarian metastases and bladder tumor clinical samples were analyzed for NQO1 and NQO2 activity, mRNA expression by semiquantitative reverse transcription-PCR, and genotype by RFLP analysis. Results: NQO1 activity was higher in the bladder cohort than in the ovarian cohort (0-283 and 0-30 nmol/min/mg, respectively; P < 0.0001). In contrast, NQO2 activity was higher in the ovarian tissue than in the bladder samples (0.15-2.27 and 0-1.14 nmol/min/mg, respectively; P = 0.0004). In both cohorts, the NQO1 C609T single-nucleotide polymorphism (SNP) was associated with ∼ 7-fold lower NQO1 activity. The NQO2 exon 3 T14055C SNP was associated with lower NQO2 activity relative to wild-type [median values of 0.18 and 0.37 nmol/min/mg in the bladder samples (P = 0.007) and 0.82 and 1.16 nmol/min/mg in the ovarian cohort (P = 0.034)]. Conclusion: This is the first observation reporting an apparent association between an NQO2 exon 3 SNP and lower enzymatic activity. The high NQO2 activity of intraperitoneal ovarian metastases relative to other tissues indicates a potential for tretazicar therapy in the treatment of this disease. In contrast, the low level of NQO1 activity and expression relative to other tissues suggests that NQO1-directed therapies would not be appropriate. © 2007 American Association for Cancer Research.
Author(s): Jamieson D, Wilson K, Pridgeon S, Margetts J, Edmondson R, Leung H, Knox R, Boddy AV
Publication type: Article
Publication status: Published
Journal: Clinical Cancer Research
Year: 2007
Volume: 13
Issue: 5
Pages: 1584-1590
ISSN (print): 1078-0432
ISSN (electronic): 1557-3265
Publisher: American Association for Cancer Research
URL: http://dx.doi.org/10.1158/1078-0432.CCR-06-1416
DOI: 10.1158/1078-0432.CCR-06-1416
PubMed id: 17332305
Altmetrics provided by Altmetric
