• Toxicological Research
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• v.20 no.3
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• pp.205-211
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• 2004

Concern that some chemicals in our environment may affect human health by disrupt-ing normal endocrine function has prompted a research on interactions of environmental contaminants with steroid hormone receptor. Toxaphene and chlordane are among the 12 persistent organic pollutants identified by the United Nations Environment Programme as requiring urgent attention. We compared the estrogenic activity of two organochlorine pesticides, toxaphene and chlordane, at estrogen receptor a (ER$\alpha$) and estrogen receptor $\beta$ (ER$\beta$). Human hepatoma cells (HepG2) were transiently transfected with rat ER$\alpha$ or ER$\beta$ plus an estrogen-responsive complement C3-luciferase (C3-Luc) reporter gene. After transfection, cells were treated with various concentrations of toxaphene and chlordane to investigate agonism or antagonism of these chemicals. Both toxaphene and chlordane were potent agonists in HepG2 cells for ER$\alpha$. In contrast, these chemicals had a minimal agonist activity with ER$\beta$ and almost abolished 17$\beta$-estradiol-induced ER$\beta$-mediated activity. Therefore, toxaphene and chlordane behaved as an ER$\alpha$ agonist and an ER$\beta$ antagonist with estrogen-responsive reporter plasmid C3-Luc, and exposure to these organochlorine pesticides could have a crictical effect on normal endocrine function.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.99-107
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• 2009

Naphthalene is bicyclic aromatic compound that is widely used in various domestic and commercial applications including lavatory scent disks, soil fumigants and moth balls. Exposure to naphthalene results in the development of bronchiolar damage, cataracts and hemolytic anemia in humans and laboratory animals. However, little information is available regarding the mechanism of naphthalene toxicity. We investigated gene expression profiles and potential signature genes in human hepatocellular carcinoma HepG2 cells and human promyelocytic leukemia HL-60 cells after 3 h and 48 h incubation with the IC$_{20}$ and IC$_{50}$ of naphthalene by using 44 k agilent whole human genome oligomicroarray and operon human whole 35 k oligomicroarray, respectively. We identified 616 up-regulated genes and 2,088 down-regulated genes changed by more than 2-fold by naphthalene in HepG2 cells. And in HL-60, we identified 138 up-regulated genes and 182 down-regulated genes changed by more than 2-fold. This study identified several interesting targets and functions in relation to naphthalene-induced toxicity through a gene ontology analysis method. Apoptosis and cell cycle related genes are more commonly expressed than other functional genes in both cell lines. In summary, the use of in vitro models with global expression profiling emerges as a relevant approach toward the identification of biomarkers associated with toxicity after exposure to a variety of environmental toxicants.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6073-6076
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• 2012

Discovery of anticancer drugs that kill or disable tumor cells in the presence of normal cells without undue toxicity is a potential challenge for therapeutic care. Several papers in the literature have emphasized the potential implications of marine products such as seaweeds which exhibit antitumor activity. Study attempts to screen the antitumor effect of Sargassum sp, against chosen cell lines such as MCF-7 (Breast cancer) and Hep-2 (Liver Cancer). Ethanol extract of Sargassum sp. was concentrated using a Soxhlet apparatus and dissolved in DMSO. In vitro cytotoxic activity of Sargassum sp at various concentrations ($100{\mu}g/ml-300{\mu}g/ml$) screened for antitumor effect against the chosen cell lines using MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a yellow tetrazole). The study documented that the percentage of cell viability has been reduced with increased concentration, as evidenced by cell death. Sargassum sp extract shows potential cytotoxic activity ($P{\leq}0.05$) with $IC_{50}$ of $200{\mu}g/ml$ and $250{\mu}g/ml$ against Hep-2 and MCF-7 cell lines respectively. The ethanol fraction of Sargassum sp induced cell shrinkage, cell membrane blebbing and formation of apoptotic bodies with evidence of bioactive components as profound influencing factors for anti-tumor effects. Further research need to be explored for the successful application of Sargassum sp as a potent therapeutic tool against cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7043-7048
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• 2014

Inhibition of heat shock protein 90 (Hsp90) leads to inappropriate processing of proteins involved in DNA damage repair pathways after DNA damage and may enhance tumor cell radio- and chemotherapy sensitivity. To investigate the potentiation of antitumor efficacy of lidamycin (LDM), an enediyne agent by the Hsp90 inhibitorgeldanamycin (GDM), and possible mechanisms, we have determined effects on ovarian cancer SKOV-3, hepatoma Bel-7402 and HepG2 cells by MTT assay, apoptosis assay, and cell cycle analysis. DNA damage was investigated with H2AX C-terminal phosphorylation (${\gamma}H2AX$) assays. We found that GDM synergistically sensitized SKOV-3 and Bel-7402 cells to the enediyne LDM, and this was accompanied by increased apoptosis. GDM pretreatment resulted in a greater LDM-induced DNA damage and reduced DNA repair as compared with LDM alone. However, in HepG2 cells GDM did not show significant sensitizing effects both in MTT assay and in DNA damage repair. Abrogation of LDM-induced $G_2/M$ arrest by GDM was found in SKOV-3 but not in HepG2 cells. Furthermore, the expression of ATM, related to DNA damage repair responses, was also decreased by GDM in SKOV-3 and Bel-7402 cells but not in HepG2 cells. These results demonstrate that Hsp90 inhibitors may potentiate the antitumor efficacy of LDM, possibly by reducing the repair of LDM-induced DNA damage.

• The Journal of Internal Korean Medicine
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• v.34 no.1
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• pp.14-30
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• 2013

Objectives : The aim of this study was to investigate whether the effects of extract from Saengkankunbi-tang and its composition that Artimisiae capillaris Herba, Crataegi Fructus, Alismatis Rhizoma, Hoelen and Raphani Semen could protect HepG2 cells from palmitic acid-induced lipotoxicity through lysosomal and mitochondrial pathways in an in vitro model. Methods : To examine the effects of the extracts from Saengkankunbi-tang and its composition that Artimisiae capillaris Herba, Crataegi Fructus, Alismatis Rhizoma, Hoelen and Raphani Semen on palmitic acid-induced lipotoxicity in HepG2 cells, we measured the contents of cell viability, cytotoxicity. Then to investigate the effects of the extract from Saengkankunbi-tang, Artimisiae capillaris Herba and Raphani Semen, we measured that triglyceride, reactive oxygen species, ATP levels, glutathione levels, cytochrome c and cathepsin B. Results : The extracts from Saengkankunbi-tang and its composition had a cell-protective function. The extracts from Saengkankunbi-tang, Artimisiae capillaris Herba and Raphani Semen controlled triglyceride over-accumulation in cells and reduced overproduction of reactive oxygen species. The extracts from Saengkankunbi-tang and Raphani Semen increased ATP and glutathione levels which had been decreased by lipotoxicity. The extracts from Saengkankunbi-tang, Artimisiae capillaris Herba and Raphani Semen reduced leakage of cytochrome c and the extracts from Saengkankunbi-tang and Raphani Semen reduced leakage of cathepsin B in lipotoxicity. Conclusions : These results show that the extracts from Saengkankunbi-tang and its composition that Artimisiae capillaris Herba and Raphani Semen have cell protective effects on palmitic acid-induced lipotoxicity through lysosomal and mitochondrial pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2993-2999
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• 2014

Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5849-5854
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• 2013

Background: Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin. Methods: Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting. Results: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co-treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta. Conclusions: ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.

• Journal of Advanced Marine Engineering and Technology
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• v.34 no.6
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• pp.894-905
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• 2010

A habitat evaluation method was used to estimate the optimum suitability of the study area for the target algae. Habitat evaluation was carried out using an habitat evaluation procedure (HEP) so that the optimum suitability was quantitatively estimated for carrying out marine afforestation in the study area. According to the results of the suitability analysis, the variation of light and wave conditions according to depth showed the factors with the largest impact to involve the spatial distribution of suitable locations within the area. The total suitable area selected was calculated to be 18ha. The quality of the target algae (Ecklonia cava Kjellman) habitat was analyzed using an habitat suitability index (HSI) model of the HEP, which showed 0.55-0.907 (the maximum value being 1.0). This indicated that artificial reefs for afforestation should be installed to zonation type because the suitable area selected (The HSI value was 0.55~0.907) was distributed within the same depth line.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1025-1029
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• 2012

Objective: To determine the killing effects on extracorporeal HepG2 cells under different temperatures, pressures of permeability and lengths of treatment time. Method: According to different temperatures, pressures of permeability and lengths of treating time, extracorporeal HepG2 cells of human hepatoma cell-line were grouped to 80 groups. Cell index (CI) as the measurement of killing effect were calculated by monotetrazolium (MTT) methods, i.e., CI =1- (the OD value in treated group - the OD value in blank control group) / (mean of untreated control group - mean of blank control group). According to the factorial design, data were fed into SPSS 10.0 and analyzed by three-way ANOVA (analysis of variance). Result: Temperature, pressure of permeability and length of treating time all had effects on the CI (cell index) level. Length of treating time was the most influential factor of the three. Additionally, any two of them all had statistically significant interactive effects on the CI level. When treated for 5-30 min, destilled water at $46^{\circ}C$ stably generated the highest CI. Conclusion: The "$46^{\circ}C$-destilled water-60 min" was considered as the optimal combination of conditions which lead to highest CI. We suggest exerting celiac lavage for 15 min with stilled water at $40^{\circ}C-43^{\circ}C$ in surgical practice as a hyperthermia treatment to achieve ideal killing effects on free cancer cells, which is feasible, practical, and clinically effective.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3281-3287
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• 2016

Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF-7 > HeLa > HepG2 > NIH3T3 cells with $IC_{50}$ values of 7.33, 14.8, 37.1 and $65.4{\mu}M$, respectively, whereas PCN was cytotoxic only to HepG2 cells with $IC_{50}$ values of ${\sim}80{\mu}M$. Apoptotic cell death was confirmed by staining the cells with annexin V-FITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamin-treated MCF-7 cells in a dose response manner. Positive PI-stained cells with the typical morphology of apoptotic cells were increased dose-dependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamin-treated MCF-7, HepG2 and HeLa cells. GTN treatment in MCF-7 increased caspase-3, -8 and -9 activities while GTN-induced HeLa cells showed an increase of both caspase-3 and -9 activities. But an increased caspase-8 activity was demonstrated in GTN- and PCN-treated MCF-7 and HepG2 cells, respectively. Taken together, GTN- and PCN-induced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compound-modulated caspase activities in both intrinsic and/or extrinsic pathways.