• Title/Summary/Keyword: Phase II detoxification enzyme

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Effect of Cnidii Rhizoma on Phase II Enzyme and Ornithine Decarboxylase Activities (천궁이 Phase II 효소 유도와 Ornithine Decarboxylase 활성에 미치는 영향)

  • Shon, Yun-Hee;Kim, Mee-Kyung;Cho, Hyun-Jung;Nam, Kyung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1572-1575
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    • 2006
  • Water extract from Cnidii Rhizoma (CRW) was tested for colon cancer chemopreventive activity by measuring the induction of phase II detoxification enzyme activity [quinone reductase (QR) and glutathione S-transferase (GST)] and glutathion (GSH) levels and ornithine decarboxylase (ODC) activity in cultured human colorectal adenocarcinoma HT-29 cells. CRW inhibited cell proliferation in cultured HT-29 cells. CRW induced QR activity in a dose-dependent manner in a concentration range of 0.1${\sim}$5.0 $mg/m{\ell}$. GST activity was also induced with the treatment of CRW in HT-29 cells. In addition GSH levels was increased with CRW. CRW inhibited ODC activity, a key enzyme of polyamine biosynthesis, which is enhanced in tumor promotion. These results suggest that CRW has colon cancer chemopreventive activity by increasing phase II enzyme activity and GSH levels and inhibiting ODC activity in vitro.

Chemopreventive effects of polysaccharides extract from Asterina pectinifera on HT-29 human colon adenocarcinoma cells

  • Nam, Kyung-Soo;Shon, Yun-Hee
    • BMB Reports
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    • v.42 no.5
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    • pp.277-280
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    • 2009
  • We examined the effects of polysaccharides extracted from Asterina pectinifera on the activities of quinone reductase (QR), glutathione S-transferase (GST), ornithine decarboxylase (ODC), cyclooxygenase (COX)-2 and glutathione (GSH) levels in HT-29 human colon adenocarcinoma cells. We found that the polysaccharides extract induced QR activity in a dose-dependent manner over a concentration range of $20-60\;{\mu}g/ml$ and increased GST activity as much as 1.4-fold over controls. GSH levels were increased 1.3- and 1.5-fold with the extract at 40 and $60\;{\mu}g/ml$, respectively. The activity and protein expression of ODC in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colon cancer cells was inhibited by the extract. The polysaccharides suppressed TPA-induced prostaglandin (PG) production. These data indicate that polysaccharides from A. pectinifera increase phase II detoxification enzyme activity and inhibit ODC and COX-2 activities in HT-29 human colon adenocarcinoma cells. Consequently, this effect may contribute to the protective effect of polysaccharides from A. pectinifera against colon cancer.

Chemopreventive activity of Prunella Herba Vulgaris L. Aqua-acupuncture Solution (댑싸리하고초(夏枯草) 약침액(藥鍼液)의 암예방 활성)

  • Park Shin-Hwa;Lim Jong-Kook
    • Korean Journal of Acupuncture
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    • v.18 no.1
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    • pp.11-20
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    • 2001
  • Cancer chemoprevention refer to the use of natural or synthetic substances to prevent the initiational and promtional events that occur during the process of carcinogenesis. The effect of Prunella Herba Vulgaris L. Aqua-acupuncture Solution (PVAS) and Prunella Herba Vulgaris L. Water-extracted Solution (PVWS) on the induction of phase II detoxification enzyme (quinone reductase, Glutathione S-transferase) and inhibition of phase I enzyme (cytochrome P4501A1) and benzo[a]pyrene-DNA adduct formation was examined. PVAS is potent inducers of quinone reductase activity. Glutathione levels were increased with PVAS, in cultured murine hepatoma Hepa1c1c7 cells. In addition glutathione S-transferase levels were increased with PVAS. However, there was 45.2% inhibition in the activity of cytochrome P4501A1 enzyme with the treatment of PVAS, $5{\times}$. At concentration of $1{\times}$ and $3{\times}$ of PVAS, the binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cell was inhibited by 25.3%, 45.0%, respectively. These results suggest that PVAS has chemopreventive potential by inducing quinone reductase and glutathione S-transferase activities, increasing GSH levels, inhibiting the activity of cytochrome P4501A1 and benzo[a]pyrene-DNA adduct formation.

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Effects of Natural Products on the Induction of NAD(P)H: Quinone Reductase in Hepa 1c1c7 Cells for the Development of Cancer Chemopreventive Agents

  • Kim, Young-Mi;Chang, Il-Moo;Mar, Woong-Chon
    • Natural Product Sciences
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    • v.3 no.2
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    • pp.81-88
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    • 1997
  • NAD(P)H:quinone reductase (QR) is one of the protective phase II enzymes against toxicity that accomplishes the capacity of detoxification by modulating the effects of mutagens and carcinogens. The detoxification mechanism is that quinone reductase promotes the 2-electron reduction of quinones to hydroquinones which are less reactive. This study is to search new inducers of quinone reductase from natural products, which can be used as cancer chemopreventive agents. Plant extracts were evaluated by using quinone reductase generating system With Hepa 1c1c7 murine hepatoma cell lines for enzyme inducing properties and crystal violet staining method for the measurement of cytotoxicity provoked. We have tested approximately 106 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of natural products. The ethyl acetate fractions of Vitex rotundifolia $(fruits,\;2FC:\;12.7\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;2FC:\;10.5\;{\mu}g/ml)$, Chrysanthemum sinese $(flowers,\;2FC:\;17.4{\mu}g/ml)$ and the hexane fractions of Angelica gigas $(roots,\;2FC:\;13.2\;{\mu}g/ml)$, Smilax china $(roots,\;2FC:\;l1.9\;{\mu}g/ml)$, Sophora flavescens $(roots,\;2FC:\;16.3\;{\mu}g/ml)$ revealed the significant induction of quinone reductase in a murine hepatic Hepa 1c1c7 cell culture system.

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Effect of Cnidii Rhizoma Water Extract on Chemopreventive Enzymes for Hepatocarcinoma (천궁 물추출물이 간암예방효소계에 미치는 영향)

  • Shon, Yun-Hee;Kim, Han-Gyu;Nam, Kyung-Soo
    • Korean Journal of Pharmacognosy
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    • v.34 no.4 s.135
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    • pp.297-302
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    • 2003
  • Cnidii Rhizoma water extract (CRW) was tested for liver cancer chemopreventive potential by measuring the inhibition of phase I enzyme and benzo[a]pyrene-DNA adduct formation and induction of phase II detoxification enzymes. There was 17.0% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of 150 mg/ml CRW. At concentration of 30 mg/ml CRW, the binding of $[^3H]B[a]P$ metablites to DNA of NCTC-clone 1469 cell was inhibited by 33.3%. CRW was potent inducer of quinone reductase (QR) and glutathione S-transferase (GST) activities in cultured murine hepatoma Hepalc1c7 cells. However, hepatic glutathione (GSH) level was not influenced by CRW. These findings suggest that CRW has chemopreventive potential of liver cancer by inhibiting cytochrome P450 1A1 activity and benzo[a]pyrene-DNA adduct formation and inducing QR and GST activities.

Increase in Hepatic DT-Diaphorase Activity by Chronic Administration of Panax ginseng Extract to Mice (생쥐에서의 인삼추출액의 장기간 투여에 의한 간장 DT-Diaphorase 활성의 증가)

  • Lee, Kang-Mee;Wie, Myung-Bok;Song, Dong-Keun;Kim, Yong-Sik;Kim, Yung-Hi
    • Journal of Ginseng Research
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    • v.17 no.2
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    • pp.123-126
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    • 1993
  • Effects of chronic administration of ginseng extracts (30 or 150 mg/kg/day for 52 days, p.o.) to mice on the activities of DT-diaphorase and glutathione S-transferase (GST) in the liver and the brain were studied. The DT-diaphorase activity in the liver was increased over 2-fold at the dose of both 30 and 150 mg/kg/day, while there was no change in the activity of the enzyme in the brain. The GST activity in the liver was increased in a dose-dependent fashion up to 142% of the control value at the dose of 150 mg/kg/day. while there was no change in the activity of the enzyme in the brain. The ginseng-induced increase in the activities of these hepatic phase II drug-metabolizing enzymes which are involved in the detoxification of carcinogens, is suggested to underlie, at least in part, the anticarcinogenic activity of Panax ginseng.

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GSTT1 Null Genotype Distribution in the Kumaun Region of Northern India

  • Bag, Arundhati;Upadhyay, Saloni;Jeena, Lalit M.;Pundir, Princi;Jyala, Narayan S.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.87-89
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    • 2013
  • Glutathione S-transferases (GSTs) constitute a multigene family of multifunctional phase II metabolic enzymes. GSTT1, an important member of this group has a wide range of substrates including carcinogens. Total homozygous deletion or null genotype resulting in total lack of enzyme activity exists in populations for this enzyme. Since the null genotype may contribute to lower detoxification of carcinogens, this genotype is expected to increase cancer risk. The frequency of the GSTT1 null genotype is known to vary significantly among populations. However, little is known about its distribution in the hilly Kumaun region of northern India. Therefore, in this study, we determined the prevalence of the GSTT1 null polymorphism in the Kumaun popilation by conducting duplex PCR in 365 voluntary healthy individuals. The GSTT1 null genotype was detected in 18.4% of the individuals. Since GSTs play significant role in xenobiotic metabolism, the present data on GSTT1 genotype distribution should contribute in understanding genetic association with cancer risk in this understudied population.

Induction of Phase II Enzyme Activity by Artemisia asiatica Nakai Aqua-acupuncture Solution (애엽(艾葉) 약침액(藥鍼液)에 의한 Phase II 효소 활성 유도)

  • Yoon Sung-Mook;Cho Kyoung-Hee;Shon Yun-Hee;Nam Kyung-Soo;Lim Jong-Kook
    • Korean Journal of Acupuncture
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    • v.18 no.1
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    • pp.1-9
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    • 2001
  • Artemisia asiatica Nakai aqua-acupuncture solution (ANAS) was administered once daily for 10 days before the tumor implantation ($1{\times}10^6\;cells$). Body weight, spleen weight and the number of ascitic tumor cells were measured at 6 days after tumor implantation. The change of body weight and the survival rate of mice were observed for 21 days. It was used three biomarkers (quinone reductase, glutathione, glutathione S-transferase) to test chemopreventive potentials of ANAS. ANAS exerted antitumor activity by inhibiting the growth of Ehrlich ascites tumor cells in vivo. Mice given Ehrlich cells and ANAS at $CV_{12}$ and $BL_{18}$ had 57.1% to 49.2% survival after 21 days. Quinone reductase activity and glutathione levels were increased with ANAS. However, glutathione S-transferase level was 1.1-fold with ANAS. These results suggest that ANAS has chemopreventive potential by inducing QR activity and increasing GSH level.

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Cancer Chemopreventive Effects of Korean Seaweed Extracts

  • Lee, Saet-Byoul;Lee, Joo-Young;Song, Dae-Geun;Pan, Cheol-Ho;Nho, Chu-Won;Kim, Min-Cheol;Lee, Eun-Ha;Jung, Sang-Hoon;Kim, Hyung-Seop;Kim, Yeong-Shik;Um, Byung-Hun
    • Food Science and Biotechnology
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    • v.17 no.3
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    • pp.613-622
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    • 2008
  • Cancer chemopreventive effects can be exerted through the induction of phase II detoxification enzymes and the inhibition of inflammatory responses. In this study, the cancer chemopreventive effects and anti-inflammatory responses of 30 seaweed extracts were examined. The extracts of Dictyota coriacea and Cutleria cylindrica exhibited the high chemoprevention index, having 4.36 and 4.66, respectively. They also activated antioxidant response element at $100\;{\mu}g/mL$ by about 3-fold while did not activate xenobiotic response element. Seven seaweed extracts, Ishige okamurae, Desmarestia ligulata, Desmarestia viridis, Dictyopteris divaricata, D. coriacea, Sargassum horneri, and Sargassum yezoense, showed significant inhibition on nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production in a dose-dependant manner in $5-20\;{\mu}g/mL$. These seaweed extracts could be used as food materials for cancer chemoprevention. D. coriacea could contain potential chemopreventive agents not only that regulate genes via an ARE-dependent mechanism but also prevent the inflammation through inhibition of NO and $PGE_2$ production.

(-) Epigallocatechin gallate restores ethanol-induced alterations in hepatic detoxification system and prevents apoptosis

  • Anuradha, Carani V;Kaviarasan, Subramanian
    • Advances in Traditional Medicine
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    • v.7 no.3
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    • pp.311-320
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    • 2007
  • The present study was designed to estimate the protective effect of (-) epigallocatechin gallate (EGCG) on ethanol-induced liver injury in rats. Chronic ethanol administration (6 g/kg/day ${\times}$ 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction - aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin and ${\gamma}$-glutamyl transferase in plasma and reduction in liver glycogen. The activities of alcohol metabolizing enzymes such as alcohol dehydrogenase and aldehyde dehydrogenase were found to be altered in alcohol-treated group. Ethanol administration resulted in the induction of cytochrome p450 and cytochrome-$b_{5}$ activities and reduction of cytochrome-c reductase and glutathione-S-transferase, a phase II drug metabolizing enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by trypan blue exclusion test and induced hepatocyte apoptosis as assessed by propidium iodide staining. Treatment of alcoholic rats with EGCG restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and drug metabolizing enzymes and cyt-c-reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in alcohol + EGCG-treated rats. These findings suggest that EGCG acts as a hepatoprotective agent against alcoholic liver injury.