<p>OBJECTIVETo investigate the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a northern Chinese population.p><p>METHODSThe NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis in 193 patients with ESCC and 141 unrelated healthy controls.p><p>RESULTSThe frequency of the T allele (null) among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.86, P=0.028). The NQO1 C/C and C/T genotype distribution among ESCC patients was not significantly different from that among healthy controls (Chi-square= 2.27 and 0.127; P=0.132 and 0.721, respectively). However, the T/T genotype frequency among ESCC patients was significantly higher than that among healthy controls (Chi-square=4.39, P=0.036). The NQO1 T/T genotype significantly increased the risk for developing ESCC, compared to the combination of C/C and C/T genotypes, with the adjusted odds ratio (OR) of 1.81 (95%CI: 1.04-3.15). This increased susceptibility exhibited pronouncedly in patients with family history of upper gastrointestinal cancers (adjusted OR=2.22, 95%CI 1.18-4.17).p><p>CONCLUSIONDetermination of the NQO1 C609T genotype may be used as a stratification marker to predicate high-risk individuals for ESCC.p>
Esophageal Neoplasms ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Polymorphism, Genetic

We investigated the growth inhibitory effects of Atrina pecitinata (AP) on the proliferation in human cancer cell lines in vitro. AP was extracted with methanol which was further fractionated into four diffferent types: methanol (APMM), haxane (APMH), butanol (APMB), and aquous layers (APMA). Among various partition layers, the APMM showed the strongest cytotoxic effects on all cancer cell lines which we used. In the MTT assay of AP fractions, the growth inhibitory effects was increased in proportion to its concentration. We observed quinone reductase (QR) induced effects in all fraction layers of AP on HepG2 cells. The QR induced effects of APMM on HepG2 cell at 80 microgram/mL concentration indicated 2.0 with a control value of 1.0.
Cell Line* ; Hep G2 Cells ; Humans ; Methanol ; NAD(P)H Dehydrogenase (Quinone)

In this study, we investigated antimicrobial and cytotoxicity effects to each fraction extracted from Hizikia fusiformis (HF), which were extracted methanol (HFM)and then the extract was fractionated into four different types: hexane (HFMH), methanol (HFMM), butanol (HFMB) and aquous (HFMA) partition layers. We determined the cytotoxic effect of these layers on human cancer cells by MTT assay. Among various partition layers of HF, the HFMB and HFMM were showed the strong cytotoxic effects on cancer cell lines we used. The quinone reductase (QR) induced activity of the HFMB on HepG2 cells at 150 microgram/mL concentration was 2.63 times more effective compared to the control value of 1.0. Although further studies are needed, the present work suggests that HF maybe a chemopreventive agent for the treatment of human cancer cells.
Cell Line ; Hep G2 Cells ; Humans ; Methanol ; NAD(P)H Dehydrogenase (Quinone)

Esophageal Neoplasms ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Point Mutation ; Polymorphism, Genetic

In this study, we investigated the anticancer activity of the fin of Thunnus Thynnus (TT ). TT was extracted with methanol (TTM ), and then further fractionated into four subfractions by using solvent partition method, affording hexane (TTMH ), methanol (TTMM ), butanol (TTMB )and aquous (TTMA )soluble fractions. We determined the cyto-toxicity of these four fractions in four kind of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. The TTMM showed the strongest cytotoxic effect at the concentration of 150 microgram/mL, displaying 95% on the HepG2 cell lines and 82% on MCF-7 cell line. The morphological changes such as membrane shirinking and blebbing of cells were also observed by TTMM treatment in HT29 cell. In addition, we observed that quinone reductase (QR ) activity was elevated by only TTMM and TTMH treatments in HepG2 cell. QR activity was increased to around 2.0 and 1.8 times in TTMM and TTMH treated HepG2 cell at 100 microgram/mL, respectively, compared to that in control. Although further studies are needed, the present work could suggest that the fin of TT has a potential to be usable as a chemo-preventive agent against cancer.
Blister ; Cell Line ; Hep G2 Cells ; HT29 Cells ; Humans ; MCF-7 Cells ; Membranes ; Methanol ; NAD(P)H Dehydrogenase (Quinone)*

PURPOSE: Two types of chitosan oligosaccharides (COSs), COS I and COS II, were investigated for the effects on ascitic tumor and enzymes for cancer chemoprevention. MATERIALS AND METHODS: Chitosan oligosaccharides were administered once daily for 10 days after the tumor implantation. The change of body weight was observed for 20 days, and the survival rate of mice was determined after 21 days. Chitosan oligosaccharides were administered once daily for 10 days before the tumor implantation (1 106 cells). The number of ascitic tumor cells were measured at 6 days after tumor implantation. Chemopreventive potential of chitosan oligosaccharides was examined by the induction of quinone reductase and inhibition of cytochrome P450 1A1. RESULTS: Chitosan oligosaccharides exerted antitumor activity by inhibiting the growth of Ehrlich ascites tumor cells in vivo. Mice given Ehrlich cells and 10 or 100 mg/kg body weight of chitosan oligosaccharides had 33% survival after 21 days. Quinone reductase activity was increased with chitosan oligosaccharides. There were 26% and 33% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of COS I and COS II, respectively. CONCLUSION: These results suggest that chitosan oligosaccharides has antitumor activity and cancer chemo preventive potential by inducing QR activity and inhibiting cytochrome P450 1A1.
Animals ; Body Weight ; Carcinoma, Ehrlich Tumor ; Chemoprevention* ; Chitosan* ; Cytochrome P-450 Enzyme System ; Mice ; NAD(P)H Dehydrogenase (Quinone) ; Oligosaccharides ; Survival Rate

Oxidative damage is thought to be a major cause of the progression of dopamine (DA)rgic neurodegeneration as in Parkinson's disease. We have previously reported that tetrahydrobiopterin (BH4), an endogenous molecule required for DA synthesis, exerts oxidative stress to DA-producing cells and facilitates the production of DA quinone. It is known that aconitase, present in both mitochondrial and cytosolic forms, act as an reactive oxygen species (ROS) sensor, and that their inactivation leads to further generation of ROS. In the present study we investigated whether the BH4-associated vulnerability of DA cells might involve aconitase. In DArgic cell line CATH.a, BH4 treatment caused reduction of activity of both mitochondrial and cytosolic aconitases, and this appeared to be due to direct inactivation of the pre-existing enzyme molecules. Although most of the activity reduced by BH4 was increased upon reactivation reaction under a reducing condition, the restoration was not complete, suggesting that irreversible and covalent modification has occurred. The aconitase inactivation was exacerbated in the presence of DA and attenuated in the presence of tyrosine hydroxylase inhibitor a-methyl-p-tyrosine, suggesting the involvement of DA. The degree of inactivation increased when the cells were treated with the quinone reductase inhibitor dicoumarol and decreased in the presence of quinone reductase inducer sulforaphane. Taken together, BH4 appeared to lead to both reversible and irreversible inactivation of aconitase and that this is facilitated by the presence of DA and accumulation of DA quinone.
Aconitate Hydratase ; Benzoquinones ; Biopterin ; Cell Line ; Cytosol ; Dicumarol ; Dopamine ; NAD(P)H Dehydrogenase (Quinone) ; Oxidative Stress ; Parkinson Disease ; Reactive Oxygen Species ; Thiocyanates ; Tyrosine 3-Monooxygenase

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by CCl4 treatment to the control level. Hepatic injury induced by CCl4 was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by CCl4.
Alkanes ; Animals ; Antioxidant Response Elements ; Carbon ; Carbon Tetrachloride ; Chrysanthemum ; Glutathione Transferase ; Kidney ; Liver ; Luciferases ; Methanol ; Mice ; NAD(P)H Dehydrogenase (Quinone) ; Stomach ; Transcriptional Activation

<p>OBJECTIVETo detect the putative association between the polymorphism of human NAD(P)H: quinone oxidoreductase (NQO1) gene and Parkinson's disease(PD).p><p>METHODSPolymerase chain reaction-denaturing high performance liquid chromatography (PCR-DHPLC) was used to detect the polymorphism of monoamine NQO1 gene cDNA 609 site(C-->T). The frequencies of alleles and genotypes in different PD groups were compared with those of the control group.p><p>RESULTSIt was found that the frequencies of TT genotype in the patients with PD and in the controls were 0.226 and 0.118 respectively (P=0.004), i.e., TT genotype increased the risk of PD by 2.186-fold (P=0.005). When the patients with PD were divided into two groups by the age at onset, significant difference in the genotypic frequencies was observed only between late-onset PD group and control group (the frequencies of TT genotype being 0.260 and 0.118, P=0.001) and TT genotype increased the risk of late-onset PD by 2.627-fold(P=0.001). There were no significant differences in frequencies of alleles between different PD groups and control group.p><p>CONCLUSIONThis study revealed significant differences in genotypic frequencies between PD group and control group. The findings supported the hypothesis about an association between NQO1 gene and PD, suggesting that the age at onset of PD might be related to the putative association, and NQO1 cDNA C609T site be a risk factor for PD.p>
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chromatography, High Pressure Liquid ; Genotype ; Humans ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Parkinson Disease ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic

<p>OBJECTIVETo investigate the association between the C609T polymorphism of NADP (H): quinoneoxidoreductase 1 (NQ01) gene and decreased cognitive function and sporadic Alzheimer's disease (AD) in a community cohort.p><p>METHODSPolymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) and sequencing were used to determine the genotype of NQ01 in 110 subjects without cognitive dysfunction, 21 with cognitive dysfunction, and 65 AD patients from a community cohort.p><p>RESULTSSignificantly different distributions of C/T and T/T genotypes were found between MMSE normal and abnormal subjects (OR=2.8, 95%CI 0.96-8.18, P=0.024), and between AD patients and healthy controls (OR=3.27, 95% CI 1.54-6.94, P=0.001), respectively. The frequencies of T allele of NQ01 C609T were significantly higher in MMSE abnormal subjects and AD patients (P=0.034 and 0.005) as compared to normal controls.p><p>CONCLUSIONThe C609T polymorphism of NQ01 gene may be a genetic risk factor for cognitive dysfunction and sporadic AD in Chinese population.p>
Alzheimer Disease ; genetics ; Base Sequence ; Cognition Disorders ; genetics ; Molecular Sequence Data ; Mutation ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors ; Sequence Analysis, DNA