NAD(P)H:Quinone Oxidoreductase 1 (NQO1, DT-Diaphorase), Functions and Pharmacogenetics

Ross, David; Siegel, David

doi:10.1016/s0076-6879(04)82008-1

Cited by 229 publications

(174 citation statements)

References 111 publications

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“…radical semiquinones, but form relatively stable hydroquinones that, depending on the functional groups present, can be further stabilized by conjugation (Cadenas et al, 1992;Testa, 1995). Two electron transfers protect the cell against reactive oxygen intermediates generated by univalent reducing enzymes (Lind et al, 1990;Ross et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

et al. 2010

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Parasitic plants in the Orobanchaceae develop haustoria in response to contact with host roots or chemical haustoriainducing factors. Experiments in this manuscript test the hypothesis that quinolic-inducing factors activate haustorium development via a signal mechanism initiated by redox cycling between quinone and hydroquinone states. Two cDNAs were previously isolated from roots of the parasitic plant Triphysaria versicolor that encode distinct quinone oxidoreductases. QR1 encodes a single-electron reducing NADPH quinone oxidoreductase similar to z-crystallin. The QR2 enzyme catalyzes two electron reductions typical of xenobiotic detoxification. QR1 and QR2 transcripts are upregulated in a primary response to chemical-inducing factors, but only QR1 was upregulated in response to host roots. RNA interference technology was used to reduce QR1 and QR2 transcripts in Triphysaria roots that were evaluated for their ability to form haustoria. There was a significant decrease in haustorium development in roots silenced for QR1 but not in roots silenced for QR2. The infrequent QR1 transgenic roots that did develop haustoria had levels of QR1 similar to those of nontransgenic roots. These experiments implicate QR1 as one of the earliest genes on the haustorium signal transduction pathway, encoding a quinone oxidoreductase necessary for the redox bioactivation of haustorial inducing factors.

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Section: Discussionmentioning

confidence: 99%

“…This class of quinone reductases is best typified by the mammalian quinone reductase NQOR or DT-diaphorase (Ross et al, 2004). These enzymes reduce quinones by a two-electron transfer mechanism that does not generate the semiquinone or associated ROS (Testa, 1995).…”

Section: Discussionmentioning

confidence: 99%

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

et al. 2010

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“…Moreover, the inverse relationship between NQO1 specific activity and TB-sensitivity (LD 50 ) was also observed in various non-melanoma human cancer cell lines. Human MIA PaCa-2 pancreatic carcinoma cells, known to express high levels of active NQO1 [43], displayed high PRC-sensitivity, whereas human MDA-MB231 breast carcinoma cells known to constitutively express an inactive NQO1 mutant (NQO1*2/*2) were PRC-resistant [44]. In contrast, PRC-resistant normal human Hs27 and CF3 dermal fibroblasts (data not shown) displayed low basal NQO1 activity as summarized in Table 1.…”

Section: Nqo1-modulation Of Prc-induced Cancer Cell Deathmentioning

confidence: 99%

NQO1-activated phenothiazinium redox cyclers for the targeted bioreductive induction of cancer cell apoptosis

Wondrak

2007

Free Radical Biology and Medicine

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Altered redox signaling and regulation in cancer cells represent a chemical vulnerability that can be targeted by selective chemotherapeutic intervention. Here, we demonstrate that 3,7-diaminophenothiazinium-based redoxcyclers (PRC) induce selective cancer cell apoptosis by NAD (P)H:quinone oxidoreductase (NQO1)-dependent bioreductive generation of cellular oxidative stress. Using PRC lead compounds including toluidine blue against human metastatic G361 melanoma cells, apoptosis occurred with phosphatidylserine-externalization, loss of mitochondrial transmembrane potential, cytochrome C release, caspase-3 activation, and massive ROS production. Consistent with reductive activation and subsequent redoxcycling as the mechanism of PRC cytotoxicity, co-incubation with catalase achieved cell protection, whereas reductive antioxidants enhanced PRC-cytotoxicity. Unexpectedly, human A375 melanoma cells were resistant to PRCinduced apoptosis, and PRC-sensitive G361 cells were protected by preincubation with the NQO1-inhibitor dicoumarol. Indeed, NQO1 specific enzymatic activity was nine fold higher in G361 than in A375 cells. The critical role of NQO1 in PRC-bioactivation and cytotoxicity was confirmed, when NQO1-transfected breast cancer cells (MCF7-DT15) stably overexpressing active NQO1 displayed strongly enhanced PRC-sensitivity as compared to vector-control transfected cells with base line NQO1 activity. Based on the known overexpression of NQO1 in various tumors these findings suggest the feasibility of developing PRC lead compounds into tumor-selective bioreductive chemotherapeutics.

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“…A number of single nucleotide polymorphisms (SNPs) have been discovered in this gene (Nebert et al, 2002), of which rs1800566 polymorphism, a C-to-T transition at nucleotide position 609 in exon 6, has been studied by various researchers. Genotype-phenotype studies demonstrated that this kind of polymorphism is associated with a decreased activity of NQO1 enzymatic activity and shows a phenotypic gene-dose effect (Siegel et al, 1999;Basu et al, 2004;Ross et al, 2004). Because of this SNP's functional consequence, many case-control studies were conducted to evaluate the association of NQO1 rs1800566 polymorphism with bladder cancer risk.…”

Section: Research Articlementioning

confidence: 99%

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

Guo¹,

Feng²

2012

Asian Pacific Journal of Cancer Prevention

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NAD(P)H:Quinone Oxidoreductase 1 (NQO1, DT-Diaphorase), Functions and Pharmacogenetics

Cited by 229 publications

References 111 publications

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

NQO1-activated phenothiazinium redox cyclers for the targeted bioreductive induction of cancer cell apoptosis

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

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