• Journal of Microbiology and Biotechnology
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• v.12 no.3
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• pp.470-475
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• 2002

In the course of screening for a novel cell cycle inhibitor, a potent Cdk 1 inhibitor, HY558, was found from the culture broth of Penicillium minioluteum F558 isolated from a soil sample. The molecular ion of HY558 was identified at m/z 329 (MH+) with a molecular formula of $C_20H_44ON_2$. HY558 exhibited selective antiproliferative effects on various human cancer cell lines. Its $IC_50$ values were estimated to be 0.29 mM on HepG2, 0.30 mM on HeLa, 0.30 mM on HL6O, 0.33 mM on HT-29, and 0.25 mM on AGS cells. Interestingly, Hy558 demonstrated no antiproliferative effect with normal lymphocytes used as the control, and a low level of inhibition on the proliferation of A549 cancer cells. A flow cytometric analysis of HepG2 cells revealed an appreciable arrest of cells at the G1 and G2/M phases of the cell cycle following treatment with Hy558. furthermore, DNA fragmentation due to apoptosis was observed in HeLa cells treated with 0.46 mM of HY558.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.947-953
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• 2004

The antioxidative and hepatoprotective potentials of two anthraquinones, alaternin (2-hydroxy-emodin) and emodin, to scavenge and/or inhibit hydroxyl radicals generated by the Fenton reaction and to protect tacrine-induced cytotoxicity in human liver derived HepG2 cells were evaluated, respectively. The inhibitory activity on hydroxyl radical generated in a cell-free chemical system (FeSO$_4$/$H_2O$$_2$) was investigated by a fluorescence spectrophotometer using a highly fluorescent probe, 2$^1$,7$^1$-dichlorofluorescein. The hydroxyl radical scavenging activity was determined by electron spin resonance spectroscopy using 5,5-dimethy-1-pyrroline-N-oxide as hydroxyl radicals trapping agents. Tacrine-induced HepG2 cell toxicity was determined by a 3-［4,5-dimethylthiazole-2yl］-2,5-diphenyltertrazolium bromide assay. Although the scavenging activity of alaternin on hydroxyl radical was similar to that of emodin in dose-dependent pat-terns, the inhibitory activity exhibited by the former on hydroxyl radical generation was stron-ger than that of the latter, with $IC_{50}$/ values of 3.05$\pm$0.26 $\mu$M and 13.29$\pm$3.20 $\mu$M, respectively. In addition, the two anthraquinones, alaternin and emodin showed their hepatoprotective activ-ities on tacrine-induced cytotoxicity, and the EC$_{50}$ values were 4.02 11M and 2.37 $\mu$M, respec-tively. Silymarin, an antihepatotoxic agent used as a positive control exhibited the EC$_{50}$ value of 2.00 $\mu$M. These results demonstrated that both alaternin and emodin had the simultaneous antioxidant and hepatoprotective activities.ies.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.36-41
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• 2010

This study was conducted to investigate the effects of fermented ginseng extract by mushroom mycelia on antiproliferation of cancer cells. Phellinus linteus, Ganoderma lucidum, and Hericium erinaceum mycelia were inoculated to ginseng. The effects of fermented ginseng extract on antiproliferation of stomach (MKN-45), colon (HCT116), mammary (MCF-7), lung (NCIH460), prostate (PC-3), and liver (HepG2) cancer cells were investigated by MTT assay. Fermented ginseng extract showed significant antiproliferation effects compared with fresh ginseng extract. Fermented ginseng extract by P. linteus, G. lucidum, and H. erinaceum mycelia showed growth-inhibitory effect of 44.50, 17.75 and 43.98% viability at 1.5 mg/mL on the MKN-45 cell line, 62.86, 3.73, and 54.55% at 1.5 mg/mL on the HCT116 cell line, 41.81, 7.01, and 37.84% at 1.5 mg/mL on the MCF-7 cell line, 53.52, 5.31, and 35.27% at 1.5 mg/mL on the NCIH460 cell line, 35.05, 3.07, and 44.29% at 1.5 mg/mL on the PC-3 cell line, and 59.57, 6.34, and 4.97% at 1.5 mg/mL on the HepG2 cell line, respectively. These results indicated that fermented ginseng by G. lucidum mycelium showed the highest antiproliferation effect against various cancer cells.

• Food Science of Animal Resources
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• v.38 no.2
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• pp.350-361
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• 2018

Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6581-6589
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• 2015

Background: Previously, stingless bee (Trigona spp.) products from East Kalimantan, Indonesia, were successfully screened for in vitro antiproliferative activity against human cancer derived cell lines. It was established that propolis from T. incisa presented the highest in vitro cytotoxicity against the SW620 colon cancer cell line (6% cell survival in $20{\mu}g/mL$). Materials and Methods: Propolis from T. incisa was extracted with methanol and further partitioned with n-hexane, ethyl acetate and methanol. The in vitro cytotoxicity of the extracts was assessed by the MTT assay against human colon (SW620), liver (Hep-G2), gastric (KATO-III), lung (Chago) and breast (BT474) cancer derived cell lines. The active fractions were further enriched by silica gel quick column, absorption and size exclusion chromatography. The purity of each fraction was checked by thin layer chromatography. Cytotoxicity in BT-474 cells induced by cardanol compared to doxorubicin were evaluated by MTT assay, induction of cell cycle arrest and cell death by flow cytometric analysis of propidium iodide and annexin-V stained cells. Results: A cardol isomer was found to be the major compound in one active fraction (F45) of T. incisa propolis, with a cytotoxicity against the SW620 ($IC_{50}$ of $4.51{\pm}0.76{\mu}g/mL$), KATO-III (IC50 of $6.06{\pm}0.39{\mu}g/mL$), Hep-G2 ($IC_{50}$ of $0.71{\pm}0.22{\mu}g/mL$), Chago I ($IC_{50}$ of $0.81{\pm}0.18{\mu}g/mL$) and BT474 (IC50 of $4.28{\pm}0.14{\mu}g/mL$) cell lines. Early apoptosis (programmed cell death) of SW620 cells was induced by the cardol containing F45 fraction at the $IC_{50}$ and $IC_{80}$ concentrations, respectively, within 2-6 h of incubation. In addition, the F45 fraction induced cell cycle arrest at the G1 subphase. Conclusions: Indonesian stingless bee (T. incisa) propolis had moderately potent in vitro anticancer activity on human cancer derived cell lines. Cardol or 5-pentadecyl resorcinol was identified as a major active compound and induced apoptosis in SW620 cells in an early period (${\leq}6h$) and cell cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancer chemotherapy.

• Herbal Formula Science
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• v.31 no.4
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• pp.283-293
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• 2023

Objectives : Native to East Asia, Japan, and Korea, Cinnamomum japonicum Siebold (CJ) is renowned for its aromatic leaves and bark. We previously assessed the antioxidant activity of fractionated CJ branches (CJB:70% EtOH extract), including hexane (CJB1), chloroform (CJB2), ethyl acetate (CJB3), butanol (CJB4), and water (CJB5). Our findings revealed that CJB3 exhibited the highest antioxidant activity. Here, we aimed to investigate whether CJB3 possesses cytoprotective effects and induces the activity of antioxidant enzymes in hepatocytes. Methods : As HepG2 cells were the first to exhibit the key characteristics of hepatocytes, we investigated the hepatoprotective effects of CJB3 on HepG2 cells. Results : Before conducting the cell experiment, we checked that CJB3, up to a concentration of 100 ㎍/mL, did not exhibit cytotoxicity toward HepG2 cells. ROS production increased because of t-BHP treatment decreased in a concentration-dependent manner upon CJB3 treatment. We confirmed that CJB3 inhibited t-BHP-induced cell death. CJB3 was found to reverse the expression of proteins associated with t-BHP-induced apoptosis. We also observed that CJB3 induced Nrf2 phosphorylation and the nuclear translocation of Nrf2. And, CJB3 treatment caused a time-dependent enhancement of GCL and NQO1 protein expression. We further confirmed that CJB3 increased the expression of Nrf2 target genes, and this effect was associated with the activation of JNK, p38, and AMPK. Conclusion : CJB3 prevents t-BHP-induced oxidative stress and apoptosis and enhances the expression of Nrf2 target genes via JNK, p38, and AMPK activation. These results suggest that CJB3 is a promising candidate for the treatment of liver diseases.

• Journal of Nutrition and Health
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• v.31 no.4
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• pp.799-808
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• 1998

To investigate the antitumor activity of mugwort (Artemisia princeps Pampan), petroleum ether extract of mugwork was partially purified by a silica gel chromatography. Among several fractions, the fraction which was obtained under the elution with acetone, showed potent cytotoxicity against mouse leukemia cell line(Ll210), human colon cancer cell line (HCT-48) and human hepatoma cell line (Hep G2) , but was less effective with normal cell line(mouse embryo cell). Acetone fraction appeared to be glycolipid by Benedict test and the major fatty acids of the lipid were C16 ; 0 , C 18: 3by GC/MS analysis.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.1-6
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• 1999

To evaluate cytotoxic effect and topoisomerase I inhibition activity of Caesalpinia sappan L., both water and methanol extracts were examined using in vitro assay. The cytotoxic effect of Caesalpinia sappan L. examined using MTT and SRB assay and $IC_{50}$ values were measured against U937, HL60, HepG2, SNU-1, SNU-16 cancer cell lines. Among them the representative cytotoxic results are shown as follows; water extract (U937=13.39 ${\mu}g/ml$, HL60=8.65 ${\mu}g/ml$, HepG2=38.48 ${\mu}g/ml$, SNU-1=7.72 ${\mu}g/ml$, SNU-16=25.49 ${\mu}g/ml$), methanol extract (U937=13.35 ${\mu}g/ml$, HL60=9.43 ${\mu}g/ml$, HepG2=25.67 ${\mu}g/ml$, SNU-1=8.37 ${\mu}g/ml$, SNU-16=28.64 ${\mu}g/ml$). The inhibitory concentration of DNA topoisomerase I activity against water extract was 100 ${\mu}g/ml$ and the inhibitory concentration of DNA topoisomerase I against methanol extract was 400 ${\mu}g/ml$.

• Korean Journal of Food Science and Technology
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• v.40 no.6
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• pp.696-701
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• 2008

The objective of this study was to determine whether Codonopsis lanceolata or Platycodon grandiflorum ethyl acetate fraction (CLEA or PGEA) protect cells against sodium nitroprusside (SNP)-induced oxidative stress via the expression of various antioxidant systems. The HepG2 cells exposed for 24 hr to 0.5 mM SNP showed a reduction in the cell viability by an MTT assay. Pretreatment with CLEA and PGEA resulted in an inhibition of SNP-induced cell death. In addition, the effects of CLEA and PGEA on the expression of antioxidant systems via RT-PCR analyses was assessed. The levels of catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD) and metallothionein (MT)-1A mRNA were increased after 24 hr of CLEA exposure. The levels of Mn superoxide dismutase CAT, G6PD, MT-1A, and MT-2A mRNA were increased after PGEA treatment. In conclusion, CLEA and PGEA exert indirect antioxidant effects, perhaps via the induction of a variety of antioxidant systems which, may protect cells against oxidative stress.

• Korean Journal of Environmental Agriculture
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• v.28 no.4
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• pp.462-467
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• 2009

Exposure of formaldehyde (FA), one of the major compounds in pesticides and in the onset of sick house syndrome, has been implicated in the development of diverse diseases. Liver is a very important organ to body metabolism and drug detoxification. Apotosis of hepatocytes is associated with the onset of liver diseases such as hepatitis. However, the apoptotic effect of FA in hepatocytes is not clear. Therefore, this study was conducted to investigate the effect of FA on the apoptosis in HepG2 cells, a human hepatocyte cell line. As a result, FA (> $500\;{\mu}M$) decreased cell viability and increased lactate dehydrogenase activity in HepG2 cells, which was blocked by the treatment of vitamin E and N-acetylcysteine (NAC). In addition, FA decreased glutathione (GSH) contents and Bcl-2 levels, while increasing lipid peroxide formation and Bax levels. It also cleaved caspase-3 form, which was blocked by the treatment of vitamin E and NAC. It is insisted that FA induced apoptosis via oxidative stress in human hepatocytes.