• Journal of Life Science
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• v.26 no.2
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• pp.174-180
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• 2016

Dicumarol is a coumarin derivative isolated from sweet clover (Melilotus alba), and has anti-coagulant activity with the inhibitory activity of NAD(P)H quinone oxidoreductase1 (NQO1). NQO1 catalyzes the two-electron reduction of quinones to hydroquinones. Dicumarol competes with NAD(P)H for binding to NQO1, resulting in the inhibition of NQO1 enzymatic activity. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. The expression of MMPs is regulated by cytokines and signal transduction pathways, including those activated by phorbol myristate acetate (PMA). However, the effects of dicumarol on metalloproteinase (MMP)-9 expression and activity are not investigated here. This study investigated whether dicumarol inhibits MMP-9 expression and activity in PMA-treated human renal carcinoma Caki cells. Dicumarol markedly inhibited the PMA-induced MMP-9 mRNA expression and MMP-9 activity. NF-κB and AP1 promoter activity, which is important in MMP-9 expression, also decreased in dicumarol-treated cells. Furthermore, dicumarol markedly suppressed the ability of PMA-mediated migration in Caki cells. When the relevance of NQO1 in the dicumarol-mediated inhibitory effect on PMA-induced MMP9 activity was elucidated, knock-down of NQO1 with siRNA was found to have no effect on PMA-induced MMP9 activity, suggesting that the stimulating effect of dicumarol on PMA-induced MMP9 activity is independent of NQO1 activity. Taken together, the present studies suggested that dicumarol may inhibit PMA-induced migration via down-regulation of MMP-9 expression and activity.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.794-802
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• 2021

In this study we investigated the role and mechanism of cardamonin on IL-1β induced injury in OA. CHON-001 cells were treated with cardamonin and IL-1β and transfected with silencing nuclear factor erythroid 2-related factor 2 (siNrf2). Cell viability was detected by Cell Counting Kit-8 assay and flow cytometer assay was utilized for cell apoptosis assessment. IL-6, IL-8, TNF-α and Nrf2 mRNA expression was tested by qRT-PCR. Western blot was employed to evaluate MMP-3, MMP-13, Collagen II, Nrf2, NQO-1, NLRP3, Caspase 1 and apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) protein levels. In CHON-001 cells, IL-1β suppressed cell viability and Collagen II level while promoting cell apoptosis and expression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), MMPs (MMP-3, MMP-13), NQO-1, and NLRP3 inflammasome (NLRP3, Caspase 1 and ASC), with no significant influence on Nrf2. Cardamonin reversed the effect of IL-1β on cell viability, cell apoptosis, pro-inflammatory cytokines, MMPs, Collagen II, and NLRP3 inflammasome levels. In addition, cardamonin advanced Nrf2 and NQO-1 expression of CHON-001 cells. SiNrf2 reversed the function of cardamonin on IL-1β-induced cell apoptosis and expression of pro-inflammatory cytokines, Nrf2, NQO-1, and NLRP3 inflammasome in chondrocytes. Taken together Cardamonin inhibited IL-1β induced injury by inhibition of NLRP3 inflammasome via activating Nrf2/NQO1 signaling pathway in chondrocyte.

• KSBB Journal
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• v.16 no.5
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• pp.486-492
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• 2001

The antimutagenic mechanism of the fraction III(RG III)separated from the water extract of Rehmannia glutionosa was investigated by Escherichia. coli GW and B/r strains. RG-III treatment did not affect the ${\beta}$-galactosidase activity E. coli GW-1060, 1106, 1107 and 1105. These results indicated that RG-III did not induce RecA protein amplification and did not also prevent the proteolytic cleavage of LexA. The bio-antimutagenicity and survival effect of RG-III on 4-nitroquinoline 1-oxide(4NQO), N-methyl-N-nitor-N\`-nitrosoguanidine(MNING) were investigate by E. coli B/r strains with have different pathway of DNA repai. RG-III slightly increased the survival of 4NQO-treated WP2, WP2s, WP67, CM561, CM611 cells, but the reactivation of survival cannot ve explained by the repair mode. RG-III caused the decrease of mutagenicity and lethality treated with MNNG in ZA159 despite of the increase in WP2, WP2s, WP67, CW561, CM611. Compared with bio-antimutagenic effects of RG-III on 4NQO, greatly increased antimutagenic effects of RG-III were observed with all the E. coli B/r strains tested, but less active in ZA159. These results suggest that RG-III was identified as a blocking agent for preventing the 4NQO induced mutagenesis, and may act as chl-products.

• BMB Reports
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• v.49 no.11
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• pp.617-622
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• 2016

Oxidative stress is closely associated with various diseases and is considered to be a major factor in ischemia. NAD(P)H: quinone oxidoreductase 1 (NQO1) protein is a known antioxidant protein that plays a protective role in various cells against oxidative stress. We therefore investigated the effects of cell permeable Tat-NQO1 protein on hippocampal HT-22 cells, and in an animal ischemia model. The Tat-NQO1 protein transduced into HT-22 cells, and significantly inhibited against hydrogen peroxide ($H_2O_2$)-induced cell death and cellular toxicities. Tat-NQO1 protein inhibited the Akt and mitogen activated protein kinases (MAPK) activation as well as caspase-3 expression levels, in $H_2O_2$ exposed HT-22 cells. Moreover, Tat-NQO1 protein transduced into the CA1 region of the hippocampus of the animal brain and drastically protected against ischemic injury. Our results indicate that Tat-NQO1 protein exerts protection against neuronal cell death induced by oxidative stress, suggesting that Tat-NQO1 protein may potentially provide a therapeutic agent for neuronal diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4107-4112
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• 2012

4-Nitroquinoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, has been found to induce lipid peroxidation in vivo and in vitro. Green tea contains a high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GTP) might be expected play a protective role against 4-NQO induced lipid peroxidation and bone marrow toxicity. In the present study, a dose of 200 mg of GTP/kg b.wt/day was given orally for a week, simultaneously animals received 0.2 ml of 0.5% 4-NQO in propylene glycol (5 mg/ml) injected intramuscularly for three times/week. Oxidants and antioxidants such as malendialdehyde (MDA) and thiols, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were significantly decreased in 4-NQO induced animals except MDA, and these parameters were brought back to near normalcy on treatment with GTP. The results suggest that GTP treatment offers significant protection against 4-NQO induced lipid peroxidation and bone marrow toxicity and might be a promising potential candidate for prevention of mutations leading to cancer.

• Korean journal of food and cookery science
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• v.16 no.5
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• pp.390-393
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• 2000

Desmutagenic effects of water-soluble and ethanol-soluble extracts of dried green tea toward the mutagenicity of 4-nitroquinoline-N-oxide(4-NQO) and 3-Amino-1,4-dimethyl-5H-pyrido［4,3-b］indole(Trp-P-1) in streptomycin-dependent SD510 strains of Salmonella typhimurium TA98 were investigated. Inhibition effects toward the mutagenicity of 4-NQO and Trp-P-1 of water-soluble and ethanol-soluble extracts from green tea were high as increase of concentration of extracts. Desmutagenic effects toward 4-NQO of water-soluble and ethanol-soluble extracts from green tea harvested in May and August were up to 93% in 1,000 $\mu\textrm{g}$ of extract/plate. Desmutagenic effects toward Trp-P-1 of ethanol-soluble extracts from green tea were 53.3∼92.1%, but the effects of water-soluble extracts decreased as increase of concentration of extracts.

• Korean Journal of Food Science and Technology
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• v.28 no.4
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• pp.796-799
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• 1996

The antimutagenic properties of twenty-one strains of Bifidobacterium were examined using Salmonella typhimurium TA98 in an in vitro assay system. The mutagens utilized for testing included Trp-P-1 (3-amino-1, 4-dimethyl-$^{5}H-pyrido$ (4, 3-b) indole), benzopyrene, IQ (2-amino -3-methylimidazo [4,5-f] quinoline), and NQO. The lyophilized cells of strain showed inhibitory effect of 64, 38, 29 and 20% in average against Trp-P-1, benzopyrene, NQO and IQ, respectively. There was no marked variation between each strain or growth stage in the degree of antimutagenicity against Trp-P-1, benzopyrene and IQ. Twelve hour grown cells showed higher antimutagenicity against NQO than 5-day grown cells. The results indicate that Bifidobacterium cells had a antimutagenic effect against several well-known mutagens to some degree.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7653-7658
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• 2015

Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is part of the antioxidant defence system involved in detoxification. This study aimed to analyze the influence of NQO1 (C609T) genetic polymorphism in non small cell lung cancer (NSCLC)as a putative risk factor. Materials and Methods: Present study included 100 cases of NSCLC (adenocarcinoma) patients and 100 age and sex matched healthy controls. NQO1 (C609T) genotyping was performed by allele specific PCR for assessment of putative associations with clinical outcome and genotypes of. The association of the polymorphism with the survival of NSCLC patients' was analyzed by Kaplan-Meier method. Results: In Indian NSCLC (adenocarcinoma) patients increased risk of developing NSCLC was found to be associated with NQO1 609TT genotype [OR 3.68(0.90-14.98), RR 2.04(0.78-5.31)] for CT [OR 2.91(1.58-5.34), RR 1.74(1.23-2.44) p=0.0005 for CT], for CT+TT [ OR 3.26(1.82-5.82), RR 1.87(1.34-2.61) p<0.0001 for CT+TT]. A significant difference (p=0.0009) was observed in genotype distribution among cases and healthy controls. Patients with CT+TT genotype exhibited a significant poor overall survival compared with patients displaying homozygous CC genotype (p=0.03) and when survival independently compared with CC, TT and CT genotype was also found to be significantly associated (p=0.02). Overall median survival times were CT 6.0 months, TT 8.2 months, and CT + TT (6.4 months)]. Conclusions: The present study revealed that NQO1 CT, TT and CT+TT genotypes may be associated with clinical outcome and risk of developing NSCLC in the Indian population.

• Korean Journal of Food Science and Technology
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• v.32 no.2
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• pp.417-423
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• 2000

Lactobacillus plantarum KLAB21 isolated from Kimchi has been reported to produce antimutagenic subtance(s) in the culture medium. In this study, antimutagenic effects of the strain KLAB21 were investigated to under various culture conditions maximize the production of antimutagenic substance(s) against N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) on Salmonella typhimurium TA100 and 4-nitroquinoline-1-oxide(NQO) on S. typhimurium TA98. Glucose(2%) as a carbon source and yeast extract(1%) as a nitrogen source resulted in the highest production of the antimutagenic substance(s) against both mutagens in the culture supernatant of L. plantarum KLAB21. The most effective concentrations of bactopeptone as a nitrogen source were 1% against MNNG and 1.5% against NQO. Optimal pH of the medium, culture temperature, and shaking speed for the antimutagenic substance(s) production were pH 7.0, $37^{\circ}C$ and 150 rpm, respectively. Under the optimal condition, the antimutagenic effects of L. plantarum KLAB21 culture supernatant were 98.4% against MNNG on S. typhimurium TA100 and 57.3% against NQO on S. typhimurium TA98.

• Microbiology and Biotechnology Letters
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• v.25 no.2
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• pp.144-150
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• 1997

After DNA damage, umuDC is the only SOS operon that must be induced to promote SOS mutagenesis in Escherichia coli. The recombinant plasmid pBC401 and pBC402 were constructed to fuse the lac structural genes with promoter region of umuDC operon to induce the expression of lacZ gene by DNA damage. We transformed the plasmid pBC401 and pBC402 into E. coli MC1061, lacZ deleted strain and determined the activity of $\beta$-galactosidase for various mutagen; UV, mitomycin C (MMC), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitroqunoline-1-oxide (NQO), ethyl methanesulfonate (EMS). The $\beta$-galactosidase activities of PBC401 and pBC402 for UV, MMC, and NQO were increased in proportion to expression time until 3 hours thereafter, the activities were constant or slightly decreased. The activities for MNNG and EMS were not so high as for UV, MMC, and NQO. When MNNG and EMS were treated, $\beta$-galactosidase activity of pBC402 was slightly lower than pBC401 but when UV, MMC, and NQO were treated in pBC402, $\beta$-galactosidase activity was slightly higher than in pBC401. Therefore, the pBC402 was better than the pBC401 in terms of sensitivity for frameshift mutagen. We suggest that the plasmid pBC401 and pBC402 are easy to detect mutagens which cause frameshift mutation rather than point mutation.