• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2753-2758
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• 2014

Background: GC-binding factor 2 (GCF2) is a transcriptional regulator that represses transcriptional activity of the epidermal growth factor receptor (EGFR) by binding to a specific GC-rich sequence in the EGFR gene promoter. In addition to this function, GCF2 has also been identified as a tumor-associated antigen and regarded as a potentially valuable serum biomarker for early human hepatocellular carcinoma (HCC) diagnosis. GCF2 is high expressed in most HCC tissues and cell lines including HepG2. This study focused on the influence of GCF2 on cell proliferation and apoptosis in HepG2 cells. Materials and Methods: GCF2 expression at both mRNA and protein levels in HepG2 cells was detected with reverse transcription (RT) PCR and Western blotting, respectively. RNA interference (RNAi) technology was used to knock down GCF2 mRNA and protein expression. Afterwards, cell viability was analyzed with a Cell Counting Kit-8 (CCK-8), and cell apoptosis and caspase 3 activity by flow cytometry and with a Caspase 3 Activity Kit, respectively. Results: Specific down-regulation of GCF2 expression caused cell growth inhibition, and increased apoptosis and caspase 3 activity in HepG2 cells. Conclusions: These primary results suggest that GCF2 may influence cell proliferation and apoptosis in HepG2 cells, and also provides a molecular basis for further investigation into the possible mechanism at proliferation and apoptosis in HCC.

• 생명과학회지
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• 제16권7호
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• pp.1169-1173
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• 2006

본 연구는 갈파래(Ulva lactuca) 추출분획의 암세포주에 대한 세포독성 및 면역활성 효과를 조사하였다. 갈파래의 에탄올 추출물로부터 분획물의 제조는 hexane, ethyl ether, methanol, butanol, $H_2O$의 용매를 이용하여 행하였다. 인간 백혈암세포주(U937), 생쥐 신경아종세포주(NB41A3), 인체간암세포주(HepG2),큰지 신경교세포주(C6) 등에 대한 갈파래 분획물의 세포독성을 측정하였다. 갈파래의 Ethyl ether 층은 4종류의 세포 모두에서 가장 높은 세포독성을 나타냈다. 또한 수층 역시 비교적 높은 세포독성을 나타냈다. 4종류의 세포 모두에서 농도의존적 경향을 나타냈다. 갈파래 분획물의 큰쥐 대식세포주(RAW 264.7)에 대한 면역활성 효과도 조사하였다. 갈파래 추출물의 5가지 분획물 모두에서 농도의존적으로 NO 생산을 활성화시켰다. 이러한 결과들로 잔파래가 항암 덴 면역활성을 나타내는 천연 소재개발에 있어 유용한 후보가 될 수 있을 것으로 사료된다.

• Molecular & Cellular Toxicology
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• 제4권1호
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• pp.52-60
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• 2008

In order to investigate whether the particles reduced to almost nano grade might affect the chemical and physical properties of organic materials, whole Korean Black-Red Ginseng was pulverized into almost nano size and then ginsenosides, minerals, carbohydrates, lipids and proteins in the ultrafine particles were compared with those in the regular particles as control. The mean size of the ultrafine particles was in the 350 nm range, while that of the regular particles was $127{\mu}m$. More ginsenosides, minerals, carbohydrates, lipids and proteins were detected in the ultrafine particles than in the regular particles. Interestingly, more lipids from the ultrafine particles dissolved in the water than those from the regular particles in the ethanol. Absorption and transport of carbohydrate, lipid or antioxidant activity across the intestinal wall using everted intestine sacks of mice was also enhanced by particle size reduction at the almost nano scale. More cytotoxic effect against hepatoma cell growth by ultrafine particles was also found. These results could be used as the basic data for the understanding and evaluation of the effects of organic nanomaterials on the human health.

• 생약학회지
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• 제38권4호
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• pp.400-402
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• 2007

Tacrine is an acetylcholinesterase inhibitor that is approved for the treatment of Alzheimer's disease. However, tacrine treatment for Alzheimer's disease results in reversible hepatotoxicity in 30-50% of patients, which seriously limits its clinical use. Accordingly, the identification of constituents in natural products that have protective effects on tacrine-induced hepatotoxicity would be valuable. In the present study, an immortalized human hepatoma cell line, HepG2 was employed to screen for agents that protect against tacrine-induced hepatotoxicity. The bioassay-guided fractionation of water extract of Cassiae Semen furnished two anthraquinones, aurantio-obtusin (1) and obtusifolin (2). Compounds 1 and 2 showed hepatoprotective effects with the protection ratio values of 55.3 +/- 0.5% and 41.2 +/- 0.8% at $160{\mu}M$, respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제6권4호
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• pp.187-191
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• 2002

Tamoxifen, an antiestrogen, has previously been shown to induce apoptosis in HepG2 human hepatoblastoma cells through activation of the pathways independent of estrogen receptors, i.e., intracellular $Ca^{2+}$ increase and generation of reactive oxygen species (ROS). However, the mechanism of tamoxifen to link increased intracellular $Ca^{2+}$ to ROS generation is currently unknown. Thus, in this study we investigated the possible involvement of calmodulin, a $Ca^{2+}$ activated protein, and $Ca^{2+}$/calmodulin-dependent protein kinase II in the above tamoxifen-induced events. Treatment with calmodulin antagonists (calmidazolium and trifluoroperazine) or specific inhibitors of $Ca^{2+}$/calmodulin-dependent protein kinase II (KN-93 and KN-62) inhibited the tamoxifen-induced apoptosis in a dose-dependent manner. In addition, these agents blocked the tamoxifen-induced ROS generation in a concentration-dependent fashion, which was completely suppressed by intracellular $Ca^{2+}$ chelation. These results demonstrate for the first time that, despite of its well-known direct calmodulin-inhibitory activity, tamoxifen may generate ROS and induce apoptosis through indirect activation of calmodulin and $Ca^{2+}$/calmodulin-dependent protein kinase II in HepG2 cells.

• Journal of Microbiology and Biotechnology
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• 제22권11호
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• pp.1482-1485
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• 2012

A natural furan derivative was isolated from the methanolic extract of the fruit bodies of Fomitiporia ellipsoidea. Its chemical structure was elucidated as methyl 3,5-dioxo-1,3,5,7-tetrahydrobenzo[1,2-c:4,5-c']difuran-4-carboxylate by means of extensive NMR and MS data analysis, and named as fomitiporiaester A (1). Compound 1 showed significant antitumor activity to hepatoma $H_{22}$ in vivo, and the inhibition rates were 42.94%, 49.17%, and 58.15% at concentrations of 5, 10, and 20 mg/kg, respectively. Compound 1 showed weak cytotoxic activities against the human hepatoblastoma (HepG-2) and human oophoroma (Skov 3) cell lines with$IC_{50}$ values of more than $100{\mu}M$.

• 생약학회지
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• 제34권4호통권135호
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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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• 제14권7호
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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.

• 한국동물위생학회지
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• 제22권2호
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• pp.135-149
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• 1999

This study was concerned with assessment of dietynitrosamine (DEN) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. The changes of hepatic morphology in rats(Sprague-Dawley) were detected by hematoxylin-eosin stain and immunohistochemistry(PCNA). The results were as follows ; 1. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake. were observed in rats 7 weeks after DEN administration. 2. Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. 3. Numerous vacuoles were showed on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were showed. 4. Several proliferative small round cells were shown on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. 5. PCNA-positive cells were showed on the vacuolated portal areas and peripheral areas of hepatic lobules. Maximal positivity was 23.6% in the areas of small round cells. In conclusion, this result confirmed that the DEN was one of the potent hepatocarcinogens. In histopathological analysis, the altered foci, hyperplastic nodules, neoplastic nodules, adenomas and carcinomas were observed in liver tumors induced by administration of DEN in rats.

• 한국동물위생학회지
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• 제22권1호
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• pp.61-70
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• 1999

This study is concerned with assessment of diethylnitrosamine(DEN) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate the changes of liver-specific enzyme activities in rats (Sprague-Dawley) by ad libitum feeding of DEN. And also, as another objective index in urine, the level of urinary biopterin was measured by high performance liquid chromatography(HPLC) method. The results were as follows ; 1. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 7 weeks after DEN administration. 2. The body and liver weights were significantly(p<0.05) decreased in rats 11 weeks after DEN administration. 3. The ratio of liver weight to body weight was rather stable and not significantly decreased in the all treatment groups. 4. The liver specific enzyme activities(AST, ALT,$\gamma$-GTP) were significantly(p<0.05) increased in all treatment groups compared to control group. 5. Compared to normal level, urine biopterin level was significantly (p<0.05) increased in all treatment groups(p<0.05). In conclusion, this result confirmed that the DEN was one of the potent hepatocarcinogens. In experimental model of rats exposed to DEN, the results indicated that values of liver specific enzyme activities(AST, ALT, $\gamma$-GTP) and urine biopterin level could be useful complementary tumor indices.