• Proceedings of the PSK Conference
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• 2002.10a
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• pp.286.1-286.1
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• 2002

Recent industrial society has human widely exposed to PAHs that are comming from the incomplete combustion of organic material as widespread environmental contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. PAHs in the mammalian cells affect CYP 1A1 gene expression as well as other phase II drug metabolizing enzymes as UDPGT, NMOR etc. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYPIAI in human breast cancer. (omitted)

• Food Science and Biotechnology
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• v.15 no.6
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• pp.914-919
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• 2006

We investigated the catechin content in green tea leaf (GTL) and green tea seed (GTS), the antiproliferative and detoxifying phase II enzyme-inducing activities of the methanolic (80%, v/v) extracts from GTL and GTS. GTL and GTS contained $8,685{\pm}1,061$ and $108{\pm}32\;{\mu}g/g$ epigallocatechin gallate (EGCG), $11,486{\pm}506$ and $116{\pm}72\;{\mu}g/g$ epigallocatechin (EGC), $3,535{\pm}308$ and $821{\pm}95\;{\mu}g/g$ epicatechin gallate (ECG), and $1,429{\pm}177$ and $37{\pm}44\;{\mu}g/g$ epicatechin (EC), respectively. The methanolic extract of GTS showed a greater increase in quinone reductase activity and antiproliferation potential against mouse hepatoma cells than GTL extract did. GTS treatment resulted in the accumulation at sub-G1 phase of mouse hepatoma hepa1c1c7 cells as assessed by flow cytometry. Enhancement of phase II enzyme activity by GTS extract was shown to be mediated, directly or indirectly, via interaction with the antioxidant response element (ARE) sequence in the genes encoding the phase enzymes. As the catechin content in GTS was significantly lower than that in GTL, components other than catechins appear to be responsible for the anticarcinogenic activity of the seed. In summary, these results suggest that the 80% methanolic extract of GTS deserves further study to evaluate its potential as an anticarcinogenic agent and to investigate its mechanism of action.

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.461-467
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• 2005

This study was conducted to investigate the biological activity and hepatoprotective effect of DWP-04 [DDB : selenium yeast: glutathione (31.1 : 6.8 : 62.1(w/w/w)] in D-galactosamine (GaIN) intoxicated rats. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was orally administered everyday before the start of GaIN injection (400 mg/kg, ip) for two weeks and animal decapitated for 24 hrs after GaIN­injected. The activities of serum enzymes, markers of liver function, were increased in the GaIN group compared to normal group and significantly lowered in the DWP-04 pretreated group than in the GaIN group. Hepatic lipid peroxide level and activities of phase 1 enzymes were significantly higher than those of GaIN group compared to normal group and lower in the DWP-04 pretreated group than in the GaIN group, and phase II enzyme activities in liver were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Total hepatic glutathione content and glutathione biosynthesis enzymes were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Therefore, the current results indicated that DWP-04 administration alleviated the GaIN-induced adverse effect through enhancing the antioxidant enzyme activities.

• Bulletin of the Korean Chemical Society
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• v.34 no.5
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• pp.1487-1493
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• 2013

Based on the finding that the 2-aminobenzamido group of MS-275 plays a crucial role in inhibiting HDACs through chelation of zinc existing at the active site of HDAC enzymes, novel N-(2-hydroxyphenyl)arylsulfonamide derivatives were synthesized for their potential ability to inhibit HDACs and evaluated for anticancer activity against human breast cancer cell line (MCF-7). Although the synthesized arylsulfonamides have failed to significantly inhibit total HDACs activity, phenyl carbamate-linked arylsulfonamide 10 and benzyl thiocarbamate-linked arylsulfonamide 15 exhibited good anticancer activities, which were only 4.3- and 3.6-fold lower anticancer activities, respectively, than MS-275 that is undergoing phase II clinical trials. These results suggest that these compounds may act as a selective HDAC inhibitor and probably N-(2-hydroxyphenyl) sulfamoyl group may play an important role in interacting with HDAC enzymes through chelation of zinc ion.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4235-4238
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• 2013

Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25 ${\mu}M$) for 24 hours. Glucoraphanin at higher concentration (25 ${\mu}M$) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10 ${\mu}M$. Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen-metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.

• 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.

• Archives of Pharmacal Research
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• v.23 no.1
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• pp.1-16
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• 2000

Many natural products elicit diverse pharmacological effects. Using two classes of potential chemopreventive compounds, the phenolic compounds and the isothiocyanates, we review the potential utility of two signaling events, the mitogen-activated protein kinases (MAPKs) and the ICE/Ced-3 proteases (caspases) stimulated by these agents in mammalian cell lines. Studies with phenolic antioxidants (BHA, tBHQ), and natural products (flavonoids; EGCG, ECG, and isothiocyanates; PEITC, sulforaphane), provided important insights into the signaling pathways induced by these compounds. At low concentrations, these chemicals may activate the MAPK (ERK2, JNK1, p38) leading to gene expression of survival genes (c-Fos, c-Jun) and defensive genes (Phase II detoxifying enzymes; GST, QR) resulting in survival and protective mechanisms (homeostasis response). Increasing the concentrations of these compounds will additionally activate the caspase pathway, leading to apoptosis (potential cytotoxicity). Further increment to suprapharmacological concentrations will lead to nonspecific necrotic cell death. The wider and narrow concentration ranges between the activation of MAPK/gene induction and caspases/cell death exhibited by phenolic compounds and isothiocyanates, respectively, in mammalian cells, may reflect their respective therapeutic windows in vivo. Consequently, the studies of signaling pathways elicited by natural products will advance our understanding of their efficacy and safety, of which many man become important therapeuitc drugs of the future.

• Toxicological Research
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• v.17
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• pp.251-256
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• 2001

The expression of phase II detoxifying enzymes is affected by a variety of compounds and the induction of the enzymes plays an essential role in chemoprevention. A variety of phytochemicals such as sulfur-containing chemoprotective agents (SCC) may trigger cellular signals and activate phase II gene expression through ARE activation. see induces glutathione S-transferases. Studies were conducted to investigate the role of mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3-kinase) in the induction of GST (e.g. rGSTA2) by sec. We also studied the MAP kinase pathway responsible for the GST expression by see and compared that with the pathway activated by oxidative stress as a result of sulfur amino acids deprivation (SAAD). see inhibited phosphorylation of ERK1/2 although the effect of see on JNK and p38 MAP kinase was minimal. Wortmannin and LY294002. PI3-kinase inhibitors. abolished the increases in rGSTA2 mRNA and protein levels by SCC. Deprivation of cystine and methionine caused oxidative stress in H4IIE cells. as evidenced by a decrease in the reduced glutathione and an increase in prooxidant production. Electrophoretic mobility shift assay revealed that the ARE complex consisting of Nrf-1/2 and Maf proteins was activated 12~48 h. The rGSTA2 mRNA and protein levels were increased by SAAD. Activation of ARE and induction of rGSTA2 were both completely inhibited by PI3-kinase inhibitors. Inhibition of p38 MAP kinase by SB203580 prevented the ARE-mediated rGSTA2 induction. The results of this study showed that PI3-kinase might play an essential role in the ARE-mediated rGSTA2 induction by see or SAAD and that the dual MAP kinase pathways were responsible for the enzyme induction.

• YAKHAK HOEJI
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• v.37 no.2
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• pp.149-157
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• 1993

Protein methylase inhibitor which is a modulator of biological methylation has been purified and characterized from porcine liver soluble fraction by cell fractionation, Sephadex G25 chromatography, reverse phase HPLC, size exclusion HPLC. The results are summarized as follows. 1) The purified inhibitor shows apparent homogeneity, as judged by HPLC. 2) A molecular weight of the purified inhibitor which is composed of 18 amino acid residues is about 1,400 daltons. 3) A single absorption peak of ultraviolet spectrum was observed at 260nm. 4) The inhibitor was not inactivated by heating at $100^{\circ}C$ until 60min. and its activity was not influenced by treatment with digestive enzymes, such as trypsin, pepsin, pronase, chymotrypin, lysozyme, DNase, and RNase. 5) The purified inhibitor inhibited protein rnethylase I, II, III and phospholipid methyltransferase activities. 6) The purified inhibitor inhibited noncompetitively protein methylase II from porcine liver, spleen, and testis. 7) The $K_{i}$ values for protein methylase II from porcine liver, spleen, and testis were 300nM, 250nM, 297nM, respectively.