• Journal of Life Science
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• v.19 no.9
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• pp.1251-1257
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• 2009

We investigated the growth inhibitory effect of internal organs of Todarodes pacificus (TP) on proliferation in human cancer cell lines in vitro. The internal organs of TP were extracted with methanol (TPM), which was then further fractionated into four subfractions by using a solvent partition method, resulting in hexane (TPMH), methanol (TPMM), butanol (TPMB), and aqueous (TPMA) soluble fractions. We determined the cytotoxic effect of these four fractions in three kinds of cancer cell lines - HepG2, MCF-7 and HT-29 - by MTT assay. Among the four subfractions of TPM, TPMH showed the strongest cytotoxic effects at a concentration of $300{\mu}g$/ml, displaying 91.56% on the HepG2 cell line and 85.93% on the MCF-7 cell line. Morphological changes such as membrane shirinking and blebbing of cells were also observed during TPMH treatment of HepG2 cells. In addition, we also observed quinone reductase (QR) induced effect in the methanol (TPMM) layer of HepG2 cells. TPMM showed the highest induction activity of quinone reductase on HepG2 cells among the other partition layers. The QR induced effect of TPMM was determined to be 2.7 at a level of $360{\mu}g$/ml with a control value of 1.0. Although further studies are needed, the present work suggests that internal organs of Todarodes pacificus (TP) may be a chemopreventive agent for the treatment of human cells.

• Journal of Nutrition and Health
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• v.40 no.2
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• pp.147-153
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• 2007

In this study, we investigated the anticancer activity of the fin of Thunnus Thynnus (TT). TT was extracted with methanol (TTM), and then further fractionated into four subfractions by using solvent partition method, affording hexane (TTMH), methanol (TTMM), butanol (TTMB) and aquous (TTMA) soluble fractions. We determined the cytotoxicity of these four fractions in four kind of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. The TTMM showed the strongest cytotoxic effect at the concentration of 150 ${\mu}g/mL$, displaying 95% on the HepG2 cell lines and 82% on MCF-7 cell line. The morphological changes such as membrane shirinking and blebbing of cells were also observed by TTMM treatment in HT29 cell. In addition, we observed that quinone reductase (QR) activity was elevated by only TTMM and TTMH treatments in HepG2 cell. QR activity was increased to around 2.0 and 1.8 times in TTMM and TTMH treated HepG2 cell at 100 ${\mu}g/mL$, respectively, compared to that in control. Although further studies are needed, the present work could suggest that the fin of TT has a potential to be usable as a chemopreventive agent against cancer.

• 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.

• Microbiology and Biotechnology Letters
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• v.29 no.3
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• pp.181-185
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• 2001

The naturally occurring chemical indole-3-carbinol (13C), found in vegetables of the Brassica genus, is a promising anticancer agent that was shown previ- ously to induce a Gl cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. The anticancer activity of 13C and the possible mechanisms of its action were explored in a human hepatocellular carcinoma cell line, HepG2. Treatment of HepG2 cells with 13C suppressed the growth of the cells. The growth sup- pression caused by 13C ($IC_{50}$/: 444$\mu$M) was found to be partially due to its ability to stop the cell cycle in HepG2 cells. Western blot analysis for the Gl phase artiest demonstrated that the expression-levels of cyclin-dependent kinase (Cdk4, Cdk6) and cyclic D were reduced strongly after treatment of Hep72 cells with 13C (4007M) for 24- 72 hrs. Furthermore, I3C selectively abolished the expression of Cdk6 in a dose- and time-dependent manner, and accordingly, inhibited the phosphorylation of retinoblastoma. Interestingly, after the HepG2 cells reached their max- imal growth arrest, the level of the p21, a well-known Cdk inhibitor, increased significantly. Therefore, it could be considered that the Gl arrest of HepG2 cells treated with 13C was due to the indirect inhibition of Cdk4/6 activities by p21 Western blot analysis for G2/M phase arrest of demonstrated the levels of Cdc2 and cyclin Bl werer reduced dramatically after the treatment of HepG2 cells with 13C ($40\mu$M) for 24-72 hrs. flow cytometry of propidium iodide-stained HepG2 cells revealed that 13C induces a Gl (53%,72hr incubation) and G2 (25%,24hr incubation) cell cycle arrest. Thus, our observations have uncovered a previously undefined antiproliferative pathway for r3C that implicates Cdk4/6 and Cdc2 as a target for cell cycle control in human HepG2 cells. However, the 13C-medi- ated cell cycle arrest and repression of Cdk4/6 production did not affect the apoptotic induction of HepG2 cell.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.89-96
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• 2000

A human hepatoma cell line, Hep G2 cells are a reliable for the study of alcohol-induced hepatotoxicity. In this study, the author investigated the effect of an aqueous extract of Asparagus $cochinchinensis_{MERRIL}$ (Liliaceae) roots (ACAE) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. ACAE dose-dependently inhibited the EtOH-induced tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ secretion. ACAE also inhibited the EtOH and $TNF-{\alpha}-induced$ cytotoxicity. Furthermore, the author found that ACAE inhibited the $TNF-{\alpha}-induced$ apoptosis of Hep G2 cells. These results suggest that ACAE may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.640-646
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• 2005

This study was performed for the investigation of anticancer effects of Siegesbeckia glabrescens(SG) on HepG2 cells, a human hepatoma cell line. In the previous study, we examined the involvement of nitric oxide (NO) on anti-proliferative and apoptotic efficacy of SG in vascular smooth muscle cells. The possible mechanism of the apoptotic effects of SG was investigated in HepG2 cells. SG showed potent cytotoxic activity in HepG2 but not chang cells, liver normal cells. SG treatment caused morphological change such as cell shrinkage, nuclei condensation and cell blebbing in HepG2 cells. SG also increased the nitrite production of HepG2 cells in a dose-dependent manner. Furthermore, L-NNA treatment inhibited the anti-proliferative effect of SG. From RT-PCR, SG decreased Bcl-2 but no affected on Bax. Western blot for procaspase-3 and COX-2 showed that degradation of procaspase-3 protein level or inhibition of COX-2 protein expression by SG treatment. In addition, the apoptotic effect of SG was also demonstrated by DNA laddering. In conclusion, SG-induced HepG2 cells death can occur via apoptosis which was dose-dependent, and associated with apoptosis-related Bcl-2/Bax gene expressions, COX-2 inhibition, caspase-3 activation and NO pathway. These results suggest that SG is potentially useful as a chemotherapeutic/chemopreventive agent in hepatocellular carcinoma.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.158-170
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• 2018

Objectives: The objective of this study is Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) and bee venom (BV) to experimental prove comparative study of VCA and BV on the anti-cancer effect and mechanisms of action. Methods: In this study, it was examined in a human hepatocellular carcinoma cell line, Hep G2 cells. Cytotoxic effects of VCA and BV on Hep G2 cells were determined by 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay in vitro. VCA and BV killed Hep G2 cells in a time- and dose-dependent manner. Results: The apoptotic cell death was then confirmed by propidium iodide staining and DNA fragmentation analysis. The mechanisms of action was examined by the expression of anti-apoptotic proteins and activation of mitogen-activated protein kinases. Treatment of Hep G2 cells with VCA activated poly (ADP-ribose) polymerase-1 (PARP-1) known as a marker of apoptosis, and mitogen-activated protein kinases signaling pathways including SAPK/JNK, MAPK and p38. BV also activated PARP-1, MAPK, p38 but not JNK. The expression level of anti-apoptotic molecule, Bcl-X, was decreased by VCA treatment but not BV. Finally, the phosphorylation level of ERM proteins involved in the cytoskeleton homeostasis was decreased by both stimuli. Conclusion: We examined the involvement of kinase in VCA or BV - induced apoptosis by using kinase inhibitors. VCA-induced apoptosis was partially inhibited by in the presence.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.10
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• pp.1514-1519
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• 2005

This study was performed to investigate the effects of Porphyra tenera (PT) on cytotoxicity and quinone reductase (QR) activity in the cancer cells. PT was extracted with methanol and further fractionated into five different types: hexane (PTMH), ethyl-ether (PTMEE), ethylacetate (PTMEA) butanol (PTMB) and aquous (PTMA) partition layers. We determined the cytotoxic effect of these layers on C6, HepG2, MCF-7, and HT-29 cell lines by MTT assay. Among the various fractions, hexane (PTMH) of PT showed the strongest cytotoxic effect on C6, HepG2 and MCF-7 cell lines. PTMH displayed very low level of cytotoxicity at the lower concentration levels and at 300 $\mu$g/mL. PTMH resulted in 87.5$\%$ growth inhibition on C6 cell 70 $\%$ on the HepG2 cell and 89$\%$ on the MCF-7 cell, which were significantly high compared to other fractions. A 400 $\mu$g/mL PTMH concentration level, 99$\%$, 94.5$\%$ and 99$\%$ of cell growth inhibition were resulted on the same cell lines. On HT-29 cell line, both hexane (PTMH) and aqueous (PTMA) fraction of PT showed cytotoxic effects, but the Percentage was not as high as previous results tested on other cell lines such as C6 HepG2 and MCF-7 cell lines. Also, we observed quinone reductase (QR) inducing-effects in all fractions of PT on HepG2 cells. The QR inducing effects of the PTMH on HepG2 cells at 150 $\mu$g/mL concentration was 6.6 times higher than the control. Although further studies are needed, the present work suggests that PT was a potential to be used as a chemopreventive.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.107-113
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• 2013

Objective : The purpose of this study was to investigate the effect of fermented Artemisiae Argyi Folium(AAF) on some activities of human hepatoma cell, HepG2. Method : To investigate the effect of fermented Artemisiae Argyi Folium(AAF) activity on the human hepatoma cells, AAF extracts was fermented by Lactobacillus pentosus K34(AFL) and Sacchromyces cerevisiae STV89(AFS). And the effects of AFL or AFS on the activities of HepG2 cell, such as cell viability, nitric oxide(NO) production and reactive oxygen species(ROS) production, were tested. Result : Human Hepatoma Cells were incubated each for 3 hours and 24 hours. Human Hepatoma Cells treated with the extract was measured with MTT assay. Then AFL was found to be non-toxic at concentrations of 10 ug/mL(3h), 100 ug/mL(24h) or more. AFS was the same result at concentrations of more than 10 ug/mL. The extract increased ROS generation in Human Hepatoma Cells. AFL increased at concentrations of 100 ug/mL more (3h, also 10 ug/mL more) and 50 ug/mL(24h) and AFS increased both 50 ug/mL. In point of NO generation, AFL inhibited at concentrations of 10 ug/mL(3h) and 100 ug/mL(24h) more (3h, also 10 ug/mL more) and AFS also inhibited 50 ug/mL or more. Conclusion : AFL and AFS, obtained from Artemisiae Argyi Folium extracts by fermentation, reduced the NO production and increased ROS production in HepG2 cell, without cytotoxicity on HepG2 cell. The results suggested that AFL and AFS increased the immunological effects of Artemisiae Argyi Folium extracts.

• Journal of Pharmacopuncture
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• v.20 no.3
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• pp.207-212
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• 2017

Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.