• Molecules and Cells
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• v.38 no.5
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• pp.457-465
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• 2015

The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.

• The Korean Journal of Cytopathology
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• v.1 no.1
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• pp.18-26
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• 1990

CT guided percutaneous fine-needle aspiration (FNA) of the liver for both cytologic and histologic examination has great value in diagnosing liver malignancy. From March, 1986 to April, 1990, 62 patients with the clinical impression of liver malignancy underwent CT guided percutaneous FNA biopsy. Of these, 43 cases were reviewed for this study, 19 were reported to be liver cell carcinoma, 2 were adenocarcinoma, 11 were reported as anaplastic cell present, and the rest (11 cases) were negative (9) or necrotic (2). Among the 11 cases of the last group, 9 were diagnosed as liver cell carcinoma and 2 were necrotic histologically. Retrospective review, in order to clarify the cause of cytologic diagnostic error, of both cytologic and histologic slides of all cases showed discordance of 23% between these diagnoses and sensitivity is 93.9% and specificity is 90.9%. The reasons were as follows ; 1) the lack of awareness of tumor cells of well differentiated liver cell carcinoma (4 cases), 2) missed tumor cells due to too scanty cellularity (1 case), 3) improper smear (2 cases) and no tumor cell In the cytologic smears (3 cases). In such cases, at the initiation of FNA, a correct diagnosis of liver malignancy could only be made by a combination of cytologic and histologic examinations. However after three years' experience we can conclude that cytomorphologic features of liver cell carcinoma are sufficiently distinctive from other liver malignancies to be diagnostic.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.519-526
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• 2012

Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. It is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5799-5804
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• 2012

Family with sequence similarity 189, member B (FAM189B), alias COTE1, a putative oncogene selected by microarray, for the first time was here found to be significantly up-regulated in hepatocellular carcinoma (HCC) specimens and HCC cell lines. mRNA expression of COTE1 in HCC samples and cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR, while protein expression of COTE1 in HCC tissues was assessed by immunohistochemistry. In addition, invasion of HCC cells was observed after overexpressing or silencing COTE1. In the total of 48 paired HCC specimens, compared with the adjacent non-cancer tissues, the expression of COTE1 was up-regulated in 31 (p<0.01). In HCC cell lines, COTE1 expression was significantly higher than in normal human adult liver (p<0.01). Overexpression of COTE1 enhanced HCC-derived LM6 and MHCC-L cellular invasion in vitro. In contrast, COTE1 knockdown via RNAi markedly suppressed these phenotypes, as documented in LM3 and MHCC-H HCC cells. Mechanistic analyses indicated that COTE1 could physically associate with WW domain oxidoreductase (WWOX), a tumor suppressor. COTE1 may be closely correlated with invasion of hepatocellular carcinoma (HCC) cells and thus may serve as an effective target for gene therapy.

• KSBB Journal
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• v.22 no.3
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• pp.168-173
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• 2007

To clarify the usefulness of fluorescent diagnosis for cancer, we investigated the optimal method of administrating 5-aminolevulinic acid (5-ALA), 5-aminolevulinic acid methyl ester (ALA-methyl ester) by analyzing fluorescence signal of Protoporphyrin IX (PpIX) in the cultured normal and cancer cells. 5-ALA and ALA-methyl ester was injected as a photosensitizer to the cancer liver cells (HepG2) and normal liver cells (Chang). Chang and HepG2 cells were incubated with various concentrations of 5-ALA and ALA-methyl ester (0-800 ${\mu}g/mL$). The accumulation of PpIX induced by 5-ALA and ALA-methyl ester was in HepG2 and Chang. The cell viability was measured by MTT assay. Fluorescence of PpIX in HepG2 cell was excited at a wavelength ($\lambda$ = 410 nm) and showed an emission spectrum at 603.2 nm, 660.8 nm and 603.2 nm, 661.4 nm which could be related to the PpIX generation induced by the applied 5-ALA and ALA-methyl ester, respectively. The experimental results showed that fluorescence signal of PpIX was proportional to the concentration of 5-ALA and ALA-methyl ester in tumor cells, but measured with low concentration in normal cells. Another results showed that the PpIX formation rate induced by ALA-methyl ester is higher than that of 5-ALA.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.74-79
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• 2015

Objectives: Here we investigated the anti-lipogenic potential of kaurenoic acid (KA), a diterpene derived from Aralia continentalis, in a cellular model of non-alcoholic fatty liver disease. Methods: HepG2 cells were treated with palmitate for 24h to induce intracellular lipid accumulation. To assess the influence of KA on steatotic HepG2 cells, various concentration of KA was co-administered. After palmitate treatment, Intracellular triglyceride content was measured. Expression level of several lipogenic genes, sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1) were measured using Western-blot analyses or RT-PCR. Results: Palmitate markedly increased intracellular triglyceride level and expression of related lipogenic genes in HepG2 cells, and which was relieved by co-administered KA. Conclusions: It is conceivable that that KA may have a pharmacological potential to reduce lipid accumulation in non-alcoholic fatty liver disease.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.29-33
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• 1997

The effects of ursodeoxycholic acid (UDCA) and its novel derivative, named as HS-1030, on the proliferation of HepG2, human hepatocellular carcinoma cells were investigated. Whereas UDCA had no significant effect in a concentration range we have tested, HS-1030 inhibited the proliferation of HepG2 cells in a concentration dependent manner. Surprisingly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferation-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (ie., cell shrinkage, nuclear condensation and the formation of apoptotic bodies). These results suggest that HS-1030 may be a good candidate as a drug for the treatment of liver cancer.

• Journal of Pharmaceutical Investigation
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• v.17 no.2
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• pp.89-93
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• 1987

Effects of Ssang Wha Tang (SWT), a blended Chinese traditional medicine, on the pharmacokinetics of sulfobromophthalein (BSP) were studied in the rats. BSP was administered via portal vein to the control and the SWT-treated rats. The in vitro distribution of BSP to blood cells and the hemato-physiological conditions, liver weight, GOT. GPT activity were also examined. The systemic clearance $(CL_s)$ of BSP was increased with the administration of SWT, but no significant differences were observed in the liver weight and in vitro distribution of BSP to blood cells. These results suggest that the intrinsic clearance of free BSP of the liver is increased with the administration of SWT in the rats.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.98-106
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• 2010

Objective: To examine the in vitro antioxidant and hepatoprotective properties of Amomum xanthoides extract and its fractions. Methods: Methanol extract of Amomum xanthoides was fractionated into three fractions; petroleum ether fraction (PFAX), water fraction (WFAX) and ethyl acetate fraction (AFAX). The antioxidant and hepatoprotective effects of these fractions were compared by in vitro experiments. Results: The total phenols content and DPPH (1 1-Diphenyl-2-picrylhydrazyl) radical scavenging activity was found significant in AFAX when compared with other fractions (PFAX, WFAX). AFAX significantly inhibited NO production by RAW 264.7 cells in LPS-activated condition. In Hep $G_2$ cells, AFAX markedly prevented the leakage of LDH and release of AST against CCl4 challenge. Conclusion: Amomum xanthoides and especially ethyl acetate fraction have potent antioxidative and hepatoprotective properties.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.60-66
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• 2014

The aim of this study was to evaluate the antioxidant activity and protective effect of extracts from the stems and leaves of Chrysanthemum boreale (CBSL) on t-BHP induced oxidative stress in human liver cells (Chang cells). Antioxidant activities in the extracts were determined for various radical scavenging activities including ferric reducing antioxidant power, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity, and oxygen radical absorbance capacity (ORAC). CBSL showed a very good scavenging effect of DPPH radical ($IC_{50}$ $0.009{\pm}0.002$ mg/mL), alkyl radical ($IC_{50}$ $0.004{\pm}0.001$ mg/mL), and hydroxyl radical ($IC_{50}$ $6.742{\pm}0.152$ mg/mL). CBSL also showed a strong antioxidant effect in the ORAC assay. In the MTT assay on human liver cells (Chang cells), the extracts showed protective effects by increasing cell viability, decreasing ROS, and restoring mitochondria membrane potential upon t-BHP induced oxidative stress. Our findings suggest that CBSL extracts are a potential therapeutic with protective antioxidant effects upon oxidative stress.