• Title/Summary/Keyword: NQO

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Antimutagenic and Cytotoxic Effects of Kochujang Extracts Added Deep Sea Water Salt and Sea Tangle (해양심층수염 및 다시마분말 첨가 고추장추출물의 항돌연변이성 및 암세포 성장억제효과)

  • Ham, Seung-Shi;Choi, Hyun-Jin;Kim, Soo-Hyun;Oh, Hyun-Taek;Chung, Mi-Ja
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.4
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    • pp.410-415
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    • 2008
  • This study was performed to observe the antimutagenic and cytotoxic activities of methanol extract of kochujang added with sea tangle and deep sea water salts (SDK) and kochujang added with sea tangle (SK) using the Ames test and SRB assay, respectively. The direct antimutagenic effect of SDK and SK methanol extracts were examined by Ames test using Salmonella Typhimurium TA98 and TA100. In the Ames test, methanol extract of SDK and SK alone did not exhibit mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). Methanol extract of SDK ($200{\mu}g$/plate) showed approximately 71.4% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain; whereas 56.1% and 83.6% inhibitions were observed on the mutagenensis induced by 4NQO and MNNG against TA100 strain. The cytotoxic effects of SDK and SK increased with increasing sample concentration against human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human stomach adenocarcinoma (AGS), and human lung carcinoma (A549). The SDK at the concentration of 1 mg/ml showed cytotoxicities of 61.5%, 61.3%, 51.4%, 57.9% and 77.7% against HeLa, Hep3B, MCF-7, AGS and A549, respectively. In contrast 1 mg/ml treatment of SDK and SK methanol extract had only $2{\sim}38%$ cytotoxicity on human transformed primary embryonal kidney cell (293).

Calpains and Apoptosis

  • Tagliarino, Colleen;Pink, John J.;Boothman, David A.
    • Animal cells and systems
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    • v.5 no.4
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    • pp.267-274
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    • 2001
  • Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have proposed a role for calpains In apoptosis, but their patterns of activation are not well characterized. Calpains have been implicated in neutrophil apoptosis, glucocorticoid-induced thymocyte apoptosis, as well as many other apoptotic pathways. Calpain activation in apoptosis is usually linked upstream or downstream to caspase activation, or in a parallel pathway alongside caspase activation. Calpains have been suggested to be involved in DNA fragmentation (via endonuclease activation), but also as effector proteases that cleave cellular proteins involved in DNA repair, membrane associated proteins and other homeostatic regulatory proteins. Recently, our laboratory demonstrated $\mu$-calpain activation in NAD(P)H: quinone oxidoreducatse 1 (NQO1)-expressing cells after exposure to $\beta$-lapachone, a novel quinone and potential chemo- and radio-therapeutic agent. Increased cytosolic $Ca^{2+}$ in NQO1-expressing cells after $\beta$-lapachone exposures were shown to lead to $\mu$-calpain activation. In turn, $\mu$-calpain activation was important for substrate proteolysis and DNA fragmentation associated with apoptosis. Upon activation, $\mu$-calpain translocated to the nucleus where it could proteolytically cleave PARP and p53. We provided evidence that $\beta$-lapachone-induced, $\mu$-calpain stimulated, apoptosis did not involve any of the known caspases; known apoptotic caspases were not activated after $\beta$-lapachone treatment of NQO1-expressing cells, nor did caspase inhibitors have any effect on $\beta$-1apachone-induced cell death. Elucidation of processes by which $\beta$-1apachone-stimulated $\mu$-calpain activation and calpains ability to activate endonucleases and induce apoptosis independent of caspase activity will be needed to further develop/modulate $\beta$-lapachone for treatment of human cancers that over-express NQO1.

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Inhibitory Effects of Poturaca oleracea L. Extract on the Mutagenicity of Various Mutagen (각종 변이원에 대한 쇠비름 추출물의 돌연변이 억제 효과)

  • 최근표;정성원;김은정;함승시
    • Journal of the East Asian Society of Dietary Life
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    • v.7 no.4
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    • pp.527-537
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    • 1997
  • This study was performed to determine the effects of antimutagenicity of Porturaca oleracea L. in Korea. In Ames test, the ethanol extract of Poturaca oleracea L. inhibited mutagenic activity of N-methyl-N'-nitro-N-nitrosoguanidine(MNNG), , 4-nitroquinoline-1-oxide(4NQO), benzo($\alpha$)pyrene (B($\alpha$)P) and 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indole (Trp-P-1) in Salmonella typhimurium TA98 and TA100. But hot-water extract Poturaca oleracea L. only Inhibited mutagenic activity of MNNG in Salmonella typhimurium TA100, On 4NQO, the ethanol extract 100-1,600$\mu\textrm{g}$/plate of Porturaca oleracea L. showed a slight inhibitory effect of 13-48%, 4-47% in TA98 and TA100, respectively, but on MNNG, it showed higher inhibitory effect of 6-86% in TA100, And the treatment of 1,600$\mu\textrm{g}$/plate of ethanol extract of Porturacea L. had strong antimutagenicity with 74-87% inhibition against TA98 and TA100 induced by B(a)P and with 85-93% inhibition against TA98 and TA100 induced by Trp-P-1. The ethanol extract was fractionated with ether. chloroform, ethylacetate, butanol and water. Among them, most of the fraction except water fraction showed strong antimutagenicity effects against mutation induced by 4-NQO, MNNG, B(a)P and Trp-P-1. Chloroform fraction had strong antimutagenicity with 91% inhibition against TA100 induced by MNNG, diethyl etherfraction had strong antimutagenicity with 92%, 98% inhibition against TA98 and TA100 induced by 4NQO, Chloroform fraction had strong antimutagenicity with 97% inhibition against TA100 induced by B (a)P and diethyl etherfraction had strong antimutagenicity with 98% inhibition against both strain Induced by Trp-P-1, respectively.

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Polymorphisms in TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566) Genes in Thai Cervical Cancer Patients with HPV 16 Infection

  • Chansaenroj, Jira;Theamboonlers, Apiradee;Junyangdikul, Pairoj;Swangvaree, Sukumarn;Karalak, Anant;Chinchai, Teeraporn;Poovorawan, Yong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.341-346
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    • 2013
  • The risk of cervical cancer development in women infected with HPV varies in relation to the individual host's genetic makeup. Many studies on polymorphisms as genetic factors have been aimed at analyzing associations with cervical cancer. In this study, single nucleotide polymorphisms (SNPs) in 3 genes were investigated in relation to cervical cancer progression in HPV16 infected women with lesions. Two thousand cervical specimens were typed by PCR sequencing methods for TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566). Ninety two HPV16 positive cases and thirty two normal cases were randomly selected. Analysis of TP53 (rs1042522) showed a significantly higher frequency in cancer samples (OR=1.22, 95%CI=1.004-1.481, p-value=0.016) while differences in frequency were not significant within each group (p-value=0.070). The genotype distributions of p16 (rs11515 and rs3088440) and NQO1 (rs1800566) did not show any significantly higher frequency in cancer samples (p-value=0.106, 0.675 and 0.132, respectively) or within each group (p-value=0.347, 0.939 and 0.111, respectively). The results indicated that the polymorphism in TP53 (rs1042522) might be associated with risk of cervical cancer development in HPV16 infected women. Further studies of possible mechanisms of influence on cervical cancer development would be useful to manage HPV infected patients.

The NAD(P)H: Quinine Oxidoreductase 1 (NQO1) Gene 609 C>T Polymorphism is Associated with Gastric Cancer Risk: Evidence from a Case-control Study and a Meta-analysis

  • Hu, Wei-Guo;Hu, Jia-Jia;Cai, Wei;Zheng, Min-Hua;Zang, Lu;Wang, Zheng-Ting;Zhu, Zheng-Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2363-2367
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    • 2014
  • The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between gastric cancer patients and controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated a significantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84), dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratified analysis by study design demonstrated stronger associations in population-based than in hospital-based studies. And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations.

Isolation and Characterization of Lactic Acid Bacteria Producing Antimutagenic Substance from Korean Dongchimi (동치미로부터 항돌연변이 물질을 생산하는 유산균의 분리 및 특성)

  • 주길재;이창호;우철주
    • Journal of Life Science
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    • v.11 no.5
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    • pp.432-438
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    • 2001
  • Various lactic acid bacteria were isolated from Korean Dongchimi (whole radish Kimichi with added water) in order to study their antimutagenic activity. Ames test using Salmonella enterica serovar typhimurium TA98 and TA100 showed the strain DLAB19 to have the highest antimutagenic activity among the 300 isolated strains against MNNG(N-methyl-N-nitro-N-nitrosoguanidine), NPD (4-nitro-O-phenylenediamine), 4-NQO(4-nitroquinoline-1-oxide) and AFB$_{1}$(aflatoxin B$_{1}$). The strain was identified as Leuconostoc mesenteroides subsp. cremoris according to the Bergeys Mannual Systematic Bscteriology based on its morphological, cultural, physiological characteristics and biological system Antimutagenic activity of Leu. mesenteroides subsp. cremoris DLAB19 was found in the culture supernatant suggesting the bacterium secretes, the antimutagenic substance in the media. The antimutagenic activity of Leu. mesenteroides subsp. cremoris DLAB19 was reconfirmed by the spore-rec assay using spores of Bacillus subtilis H17 (Rec$^{+}$) and M45 (Rec$^{[-10]}$ ).).

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Antimutagenic Effects of Browning Products Reacted with Polyphenol Oxidase Extracted from Apple by Using SOS Chromotest (SOS Chromotest에 의한 사과의 효소갈변반응 생성물의 항돌연변이 효과)

  • Baik, Chang-Weon;Ham, Seung-Shi
    • Korean Journal of Food Science and Technology
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    • v.22 no.6
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    • pp.618-624
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    • 1990
  • The antimutagenic effects of apple enzymatic browning reaction products(AEBRP) which resulted from the reaction of catechol, hydroquinone, homocatechol, hydroxyhydroquinone and pyrogallol with polyphenol oxidase extracted from apple(Jona gold) were investigated. Test strain used in SOS spot test and SOS chromotest was E. coli PQ 37/plasmid pKM 101. In SOS spot test, all of five AEBRPs showed strong antimutagenic effects on mytomycin C(MMC), 4-nitroquinoline-1-oxide(4NQO), N-me-thyl-N'-nitro-N-nitrosoguanidlne(MNNG) as increasing concentrations of AEBRP solution. In SOS chromotest, most of AEBRPs also showed strong antimutagenic effects on MMC, MNNG, 4NQO and 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (Trp-P-1), as increasing concentration of AEBRP solution.

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Antimutagenic Effects of Boiled Water Extract and Tannin from Persimmon Leaves (감잎 열수추출물 및 감잎 탄닌의 항돌연변이 효과)

  • 박건영;문숙희
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.6
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    • pp.880-886
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    • 1995
  • Antimutagenic effects of boiled water extract and tannin from persimmon leaves were studied by using Ames test, spore rec assay and SOS chromotest. Strong antimutagenic activities toward aflatoxin B1(AFB1), dimethyl-aminobiphenyl(DMAB), N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 4-nitroquinoline-1-oxide(4-NQO) were observed when boiled water extract and tannin from the persimmon leaves were added in the Salmonella typhimurium TA 100. In spore rec assay using Bacillus subtilis H17($rec^{+}$) and M45($rec^{-}$), boiled water extract and tannin from the persimmon leaves considerably inhibited the mutagenesis induce by MNNG. In SOS chromotest using Escherichia coli PQ37, these samples also exhibited strong antimutagenic activity toward 4-NQO. The tannin was more effective than boiled water extract of persimmon leaves in the antimutagenicity tests.

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Antimutagenic Effects of Methyl Alcohol Extracts from Auricularia auricula and Gyrophora esculenta (목이 및 석이 메틸 알콜 추출물의 항돌연변이원성)

  • Ham, Seung-Shi;Kim, Deug-Ha;Lee, Deuk-Sik
    • Korean Journal of Food Science and Technology
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    • v.29 no.6
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    • pp.1281-1287
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    • 1997
  • This study was conducted to investigate the antimutagenic effects of methyl alcohol extracts from Auricularia auricula and Gyrophora esculenta on the SOS response induced by 4-nitroquinoline-1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), mitomycin C (MMC) and 3-amino-1,4- dimethyl-5H-pyrido-[4,3-b]indol (Trp-P-1) in E. coli PQ37/plasmid pKM101. In the mutagenic test on test strain, both methyl alcohol extracts did not show mutagenic activity. In the antimutagenic test, each sample strongly inhibited the mutagenecity induced by 4NQO, MNNG, MMC and Trp-P-1. Methyl alcohol extracts from Auricularia auricula and Gyrophora esculenta showed inhibitory effects of 52% and 59% against 4NQO, 49% and 58% against MNNG, 53% and 64% against MMC, and 61% and 64% against Trp-P-1, respectively. Gyrophora esculenta extracts on the antimutagenicity showed relatively higher inhibitory effects than that of Auricularia auricula.

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Antimutagenicity of Soybean Sprouts Cultured with Germanium (게르마늄 수용액으로 재배한 콩나물의 항돌연변이 효과)

  • 김은정;이경임;박건영
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.6
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    • pp.930-935
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    • 2004
  • This study was carried out to determine the antimutagenic effect of soybean sprouts cultured in water containing germanium by Ames test and SOS chromotest. Germanium significantly inhibited the mutagenicity induced by aflatoxin B$_1$ (AFB$_1$) in Salmonella typhimurium TA100 by Ames test, and 4-nitroquinoline-N-oxide (4-NQO) in SOS chromotest. Juice from germanium treated soybean sprouts (GTS) inhibited 57∼75% mutagenicity induced by AFB$_1$, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-NQO compared with 20∼48% inhibition rate of control soybean sprouts (germanium non-treated soybean sprouts, GNTS) in the Ames test. Also, methanol extracts from GTS inhibited 65% mutagenicity induced by AFB$_1$ in Salmonella typhimurium TA100, and 51% mutagenicity by 4-NQO in SOS chromotest. Therefore, it suggests that GTS has strong potential antimutagenic effect.