• Advances in Traditional Medicine
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• v.3 no.3
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• pp.141-146
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• 2003

The methanol extracts of the aerial parts, leaves and stem of Hypericum hookerianum were tested for in vitro cytotoxicity on selected normal and cancer cell lines and anti tumor activity using DLA cells. Cell viability and morphological changes were assessed. Among the three extracts tested, the stem extract of Hypericum hookerianum showed potent cytotoxicity against HEp-2 and RD cell lines. The $CTC_{50}$(concentration required to reduce viability by 50%) of this extract was found to be $2.02\;{\mu}g/ml$ for RD cell line, $10.25\;{\mu}g/ml$ for HEp-2 cell line and $100.06\;{\mu}g/ml$ for Vero cell line. In the clonogenic assay, no colony formation was observed up to a concentration of $100\;{\mu}g/ml$. In the short term cytotoxicity studies using DLA cells, 50% viability was observed in the concentration range of $50-100\;{\mu}g/ml$ for aerial parts, $100-200\;{\mu}g/ml$ for stem and more than $200\;{\mu}g/ml$ for leaf extracts of Hypericum hookerianum. In the long-term activity using HEp-2 cell line, no colony formation was observed over a concentration of 200 mg/ml for the stem extract. Hypericum hookerianum stem extract was fractionated into petroleum ether, chloroform, ethyl acetate and methanol soluble fractions. The petroleum ether and chloroform soluble fractions showed higher cytotoxic activity against HEp-2 cell line when compared to the other two fractions. The methanol stem extract of Hypericum hookerianum has the potential for further investigation in animal models to determine its anti-tumor activity and to identify its active principles.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.1
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• pp.8-12
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• 2005

This study was performed to determine the inhibitory effects on cell survival and Quinone reductase induced activity of Aster yomena (AY) on human cancer cells which, using methanol, was extracted and fractionated into five different solvent types: hexane (AYMH), ethylether (AYMEE), ethylacetate (AYMEA), butanol (AYMB) and aqueous (AYMA) partition layers. The experiment was conducted to determine cytotoxicity of various Aster yomena partition layers on HepG2, HeLa and MCF-7 cells by MTT assay. Among various partition layers of Aster yomena, A YMEE and A YMEA showed the strong cytotoxic effects on all cancer cell lines we used. The Quinone reductase (QR) induced activity on HepG2 cells, A YMH at a does of 100 $\mu$g/mL was 2.46 times more effective compared to the control value of 1.0.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4897-4902
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• 2014

Purpose: To investigate the anticancer effects and underlying mechanisms of parthenolide on HepG2 human hepatocellular carcinoma cells. Materials and Methods: Cell viability was assessed by MTT assay and cell apoptosis through DAPI, TUNEL staining and Western blotting. Monodansylcadaverin(MDC) and AO staining were used to detect cell autophagy. Cell proliferation was assessed by Ki67 immunofluorescence staining. Results: Parthenolide induced growth inhibition in HepG2 cells. DAPI and TUNEL staining showed that parthenolide could increase the number of apoptotic nuclei, while reducing the expression of the anti-apoptotic protein Bcl-2 and elevating the expression of related proteins, like p53, Bax, cleaved caspase9 and cleaved caspase3. Parthenolide could induce autophagy in HepG2 cells and inhibited the expression of proliferation-related gene, Ki-67. Conclusions: Parthenolide can exert anti-cancer effects by inducing cell apoptosis, activating autophagy and inhibiting cell proliferation.

• Journal of Life Science
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• v.21 no.7
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• pp.1046-1051
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• 2011

Diallyl disulfide (DADS), the most prevalent oil-soluble organosulfur compound in garlic, is known to have diverse biological activities, including anticarcinogenic, antiatherosclerotic, antiinflammatory, and antioxidant actions. In this study, we investigated the effect of DADS on the expression of heme oxygenase-1 (HO-1) in human liver hepatoma cell line HepG2. Treatment of HepG2 cells by DADS evoked a dose-dependent growth inhibition without significant toxicity to the cells, and also induced the expression of transcription factor Nrf2. However, DADS did not have any enhancing effect on transcription and translation of HO-1 expression in HepG2 cells. In addition, DADS efficiently blocked protein synthesis of HO-1 in HepG2 cells stimulated by CoPP or hemin. But, DADS did not decrease the content of transcripts of HO-1 gene stimulated by CoPP, with accumulation of Nrf2 and small Maf in the nucleus. Based on these results, we conclude that DADS inhibits HO-1 expression by modulation of translational level of CoPP or hemin-induced HO-1 expression in HepG2 cells.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.226-233
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• 2007

Purpose: Dual reporter gene imaging has several advantages for more sophisticated molecular imaging studies such as gene therapy monitoring. Herein, we have constructed hepatoma cell line expressing dual reporter genes of sodium iodide symporter (NIS) and enhanced green fluorescence protein (EGFP), and the functionalities of the genes were evaluated in vivo by nuclear and optical imaging. Materials and Methods: A pRetro-PN vector was constructed after separating NIS gene from pcDNA-NIS. RSV-EGFP-WPRE fragment separated from pLNRGW was cloned into pRetro-PN vector. The final vector expressing dual reporter genes was named pRetro-PNRGW. A human hepatoma (HepG2) cells were transfected by the retrovirus containing NIS and EGFP gene (HepG2-NE). Expression of NIS gene was confirmed by RT-PCR, radioiodine uptake and efflux studies. Expression of EGFP was confirmed by RT-PCR and fluorescence microscope. The HepG2 and HepG2-NE cells were implanted in shoulder and hindlimb of nude mice, then fluorescence image, gamma camera image and I-124 microPET image were undertaken. Results: The HepG2-NE cell was successfully constructed. RT-PCR showed NIS and EGFP mRNA expression. About 50% of cells showed fluorescence. The iodine uptake of NIS-expressed cells was about 9 times higher than control. In efflux study, $T_{1/2}$ of HepG2-NE cells was 9 min. HepG2-NE xenograft showed high signal-to-background fluorescent spots and higher iodine-uptake compared to those of HepG2 xenograft. Conclusion: A hepatoma cell line expressing NIS and EGFP dual reporter genes was successfully constructed and could be used as a potential either by therapeutic gene or imaging reporter gene.

• Journal of Microbiology and Biotechnology
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• v.25 no.3
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• pp.413-417
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• 2015

Recently, we isolated HY253, a novel decahydrofluorene analog with a molecular structure of 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol from the roots of Aralia continentalis, which is known as Dokwhal (獨活), a traditional medicinal herb. Moreover, we previously reported its cytotoxic activity on cancer cell proliferation in human lung cancer A549 and cervical cancer HeLa cells. The current study aimed to evaluate its detailed molecular mechanisms in cell cycle arrest and apoptotic induction in human hepatocellular carcinoma HepG2 cells. Flow cytometric analysis of HepG2 cells treated with $60{\mu}M$ HY253 revealed appreciable cell cycle arrest at the G1 phase via inhibition of Rb phosphorylation and down-regulation of cyclin D1. Furthermore, using western blots, we found that up-regulation of cyclin-dependent kinase inhibitors, such as p21^CIP1 and p27^KIP1, was associated with this G₁ phase arrest. Moreover, TUNEL assay and immunoblottings revealed apoptotic induction in HepG2 cells treated with $60{\mu}M$ HY253 for 24 h, which is associated with cytochrome c release from mitochondria, via down-regulation of anti-apoptotic Bcl-2 protein, which in turn resulted in activation of caspase-9 and -3, and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, we suggest that HY253 may be a potent chemotherapeutic hit compound for treating human liver cancer cells via up-regulation and activation of the p53 gene.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1235-1242
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• 2006

Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.

• Journal of Ginseng Research
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• v.23 no.2 s.54
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• pp.99-104
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• 1999

The effects of ginseng and cinnamon extract alone or mixture on the various cancer cell lines in vitro have been examined. Human colon cancer cell line (HT-29), human rectal cancer cell line (HRT-18) and human hepatoma cell line (HepG2) were used for the experiment. When given separately, the proliferation of all cancer cell lines was inhibited in proportion to the concentration of ginseng or cinnamon extract, respectively. Based on the cytotoxic activity, mixture of ginseng and cinnamon extract demonstrated a synergistic inhibition of cancer cell growth. The progression of cell cycle from G1 to S phase was significantly inhibited by ginseng and cinnamon mixture in the HT-29 and HRT-18 cell lines.

• Biomedical Science Letters
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• v.17 no.3
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• pp.253-260
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• 2011

Chaga mushroom (Inonotus obliquus) extract has been known to have therapeutic effects, such as anti-inflammatory, hepato-protective, anti-oxidant and anti-tumor effect. In this study, we evaluated the effects of Chaga extract on the cytotoxic actions of cisplatin in HepG2 hepatoma cells. The viability of the HepG2 cells was decreased to 10% at 3 ${\mu}M$ cisplatin and to 20% at 500 ${\mu}g$/ml Chaga extract as measured by the MTT assay. The viability of HepG2 cells co-treated with cisplatin (3 ${\mu}M$) and Chaga extract (500 ${\mu}g$/ml) was decreased to 50% in compared with the control cells. The cytotoxicity of two drugs was revealed as apoptosis characterized by the chromatic condensation, nuclear fragmentation and the cleavage of pro caspase-3 in HepG2 cells. Also, the cells treated with combination of two drugs showed synergistically the loss of mitochondrial membrane potential and increase of intracellular ROS levels. Therefore, these results suggest that the combination treatment of cisplatin and Chaga extract induces apoptotic cell death in HepG2 cells and has more potential anti-tumor effect than cisplatin alone.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10397-10400
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• 2015

Stigmalactam, an aristolactam-type alkaloid extracted from Orophea enterocarpa, exerts cytotoxicity against several human and murine cancer cell lines, but the molecular mechanisms remain elusive. The aims of this study were to identify the mode and mechanisms of human cancer cell death induced by stigmalactam employing human hepatocellular carcinoma HepG2 and human invasive breast cancer MDA-MB-231 cells as models, compared to normal murine fibroblasts. It was found that stigmalactam was toxic to HepG2 and MDA-MB-231 cells with $IC_{50}$ levels of $23.0{\pm}2.67{\mu}M$ and $33.2{\pm}4.54{\mu}M$, respectively, using MTT assays. At the same time the $IC_{50}$ level towards murine normal fibroblast NIH3T3 cells was $24.4{\pm}6.75{\mu}M$. Reactive oxygen species (ROS) production was reduced in stigmalactam-treated cells dose dependently after 4 h of incubation, indicating antioxidant activity, measured by using 2',7',-dichlorohydrofluorescein diacetate and flow cytometry. Caspase-3 and caspase-9 activities were increased in a dose response manner, while stigmalactam decreased the mitochondrial transmembrane potential dose-dependently in HepG2 cells, using 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, indicating mitochondrial pathway-mediated apoptosis. In conclusion, stigmalactam from O. enterocarpa was toxic to both HepG2 and MDA-MB-231 cells and induced human cancer HepG2 cells to undergo apoptosis via the intrinsic (mitochondrial) pathway.