• YAKHAK HOEJI
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• v.49 no.6
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• pp.505-510
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• 2005

Allylthio group of allicin and other organosulfur compounds which are isolated from garlic is considered as a pharmacophore, a key structure component of the molecule which is responsible biological activities. In the foregoing studies various 3-allylthio -6- alkoxypyridazine derivatives (K- compounds ) and 3-allylthio -6- alkylthiopyridazine derivatives(Thio-K-compounds) were synthesized and their biological activities were tested in vivo. They showed good hepatoprotective activities on the carbon tetrachloride-treated mouse and aflatoxin Bl-treated rat and chemopreventive activities on bepatocarcinoma cells in rat as expected. Now 3-allylthio-6-heterocyclylalkylaminopyridazine derivatives that the oxygen atom at 6-Position of 3-allylthio-6-alkoxypyridazine is replaced by nitrogen (N) were synthesiz ed and their activities were tested in vitro against SK-Hep-1 human liver cancer cells. They showed good chemopreventive activities on hepatocarcinoma cells.

• YAKHAK HOEJI
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• v.46 no.3
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• pp.155-160
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• 2002

Through a modification of allicin structure a disagreeable odor and chemical instability of allicin can be improved. 3-Alkoxy-6-allylthiopyridazine derivatives exhibit a superior effect for prevention and treatment of hepatic diseases induced by carbon tetrachloride and aflatoxin B1 and for prevention of human tissues from radiation. These compounds inhibit also efficiently SK-Hep-1 cell proliferation through induction of apoptosis. So another 4,5-mono- or di-substituted 3-alkyloxy-6-allylthiopyridazine derivatives were synthesized on purpose to find out SAR of allylthiopyridazine in hepatoprotective and hepatotherapeutic acitivitis and to develop more effective drug candidate.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.218.1-218.1
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• 2003

Dietary organosulfur compounds have been shown to inhibit the proliferation of tumor cells. Synthetic sulfur-containing compounds including oltipraz exert chemopreventive and hepatoprotective effects. We previously showed that synthetic allylthiopyridazine derivatives designated as K compounds induced apoptosis in SK-Hep-1 hepatocarcinoma cells (Eur. J. Cancer: 37, 2104-10, 2001). (omitted)

• Korean Journal of Food Science and Technology
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• v.34 no.4
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• pp.688-693
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• 2002

The anticarcinogenic effects of various food components have received much attention in recent years. However mechanism of anticarcinogens in food materials on cancer cells have rarely been investigated. This study was performed to investigate the effects on the cytotoxicity and quinone reductase (QR) activity of Allium tuberusum (AT) on the human cancer cells. The six partition layers which are methanol (ATM), hexane (ATMH), ethylether (ATMEE), ethylacetate (ATMEA), butaonl (ATMB) and aqueous (ATMA) of Allium tuberusum were screened for their cytotoxic effects on HepG2, MCF-7, HeLa and SK-N-MC cells by the MTT assay. Among the six partition layers, ATMEE had the strongest cytotoxic effect at concentration of $150\;{\mu}g/mL$ which resulted over 95% on HepG2, HeLa, MCF-7 and SK-N-MC cell lines. The ATMEA also showed significant cytotoxic effect on HepG2 and SK-N-MC cell lines. The ATMB showed the highest induction activity of QR on HepG2 cells among the other partition layers. QR activity of HepG2 cells, grown in the presence of ATMB at the concentration of $50\;{\mu}g/mL$, was increased by 3.9 times, compared to the control value of 1.0. Based on these results, the ATMEE and ATMB may have potentially anticarcinogenic and chemopreventive activities.

• YAKHAK HOEJI
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• v.56 no.1
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• pp.14-19
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• 2012

Nonalcoholic steatohepatitis(NASH) is serious metabolic disease related to fatty acid. According to "two hit theory", fatty acid-induced oxidative stress is important factor to progress nonalcoholic steatohepatitis from steatosis. In this study, we evaluated stearic acid induced oxidative stress in human hepatocarcinoma SK-Hep-1 cell. Cell viability, reactive oxygen species (ROS) production, glutathione (GSH), malondialdehyde and expression of antioxidant enzymes were determined at various time-points and concentrations of stearic acid. At 0.2 mM, non-toxic concentration, of stearic acid, production of ROS was significantly increased at 24 hours and the level of GSH was significantly decreased. Expression of superoxide dismutase-1 and 2 was slightly increased in 0.2 mM stearic acid at 24 hours. These results represent that the non-toxic concentration of stearic acid resulted in oxidative stress, suggesting that stearic acid may play a critical role in development of steatohepatitis.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.492-498
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• 2012

Phytochemicals have been known to exhibit potent antioxidant activity. This study examined cytoprotective effects of phytochemicals including quercetin, catechin, caffeic acid, and phytic acid against oxidative damage in SK-Hep-1 cells induced by the oxidative and non-oxidative metabolism of ethanol. Exposure of the cells to excess ethanol resulted in a significant increase in cytotoxicity, reactive oxygen species (ROS) production, lipid hydroperoxide (LPO), and antioxidant enzyme activity. Excess ethanol also caused a reduction in mitochondrial membrane potential (MMP) and the quantity of reduced glutathione (GSH). Co-treatment of cells with ethanol and quercetin, catechin, caffeic acid and phytic acid significantly inhibited oxidative ethanol metabolism-induced cytotoxicity by blocking ROS production. When the cells were treated with ethanol after pretreatment of 4-methylpyrazole (4-MP), increased cytotoxicity, ROS production, antioxidant enzyme activity, and loss of MMP were observed. The addition of quercetin, catechin, caffeic acid and phytic acid to these cells showed suppression of non-oxidative ethanol metabolism-induced cytotoxicity, similar to oxidative ethanol metabolism. These results suggest that quercetin, catechin, caffeic acid and phytic acid have protective effects against ethanol metabolism-induced oxidative insult in SK-Hep-1 cells by blocking ROS production and elevating antioxidant potentials.

• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.371-377
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• 2018

The fruits of Panax ginseng were extracted with 80% aqueous MeOH and the concentrates were partitioned into EtOAc, n-BuOH, and $H_2O$ fractions. The repeated $SiO_2$ and octadecyl $SiO_2$ column chromatographies for the EtOAc fraction led to isolation of five ginsenosides. The chemical structures of these compounds were determined as ginsenoside F1 (1), ginsenoside F2 (2), ginsenoside F3 (3), ginsenoside Ia (4), notoginsenoside Fe (5) based on spectroscopic analyses including nuclear magnetic resonance, MS, and infrared. Compounds 2-5 were isolated for the first time from the fruits of P. ginseng in this study. All isolated compounds were evaluated for cytotoxic activities against human cancer cell lines such as HCT-116, SK-OV-3, human cervix adenocarcinoma (HeLa), HepG2, and SK-MEL-5. Among them compounds 2, 4, and 5 showed significant cytotoxicity on cancer cells. Compound 2 exhibited cytotoxicity on SK-MEL-5, HepG2, and HeLa cells with $IC_{50}$ values of 82.8, 86.8, and $78.3{\mu}M$, respectively. Compound 4 showed cytotoxicity on HCT-116, SK-MEL-5, SK-OV-3, HepG2, and HeLa cells with $IC_{50}$ values of 24.5, 25.4, 26.3, 22.0, and $24.9{\mu}M$, respectively. Compound 5 did on SK-MEL-5 cell with $IC_{50}$ value of $81.7{\mu}M$. The cytotoxicity of ginsenoside 2, 4, and 5 isolated from the fruits of Panax ginseng showed strong inhibition effect against on cancer cells, all of which have a glucopyranosyl moiety on C-3.

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.360-360
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• 1998

C11, a chloride-containing VK3 analog, acts as a mediator of programmed cell death in SK-Hep-1 cell lines, but its molecular mechanisms linked to cell death are not understood. In this study, we investigated the expression of p21 gene and its relationship to apoptosis induced by C11. In SK -hep-1 cells, the addition of C11 resulted in time-dependent growth suppression and DNA fragmentation characteristics of apoptosis. p21 protein was induced during this process, while the protein level of p53 was not changed at the same condition. This apoptotic cell death with p21 induction was also observed in the Hep3B cells lacking functional p53 after treatment of C11. These results suggest that C11-induced apoptosis is associated with up-regulation of p21 protein in p53-independent pathway. Next, in order to confirm whether the p53-independent p21 induction is required for C11-induced apoptosis, we introduced the p21 gene into Hep3B. Overexpression of p21 did not affect the expression of the bcl-2 gene, but DNA fragmentation and PARa cleavage were significantly increased. These data indicate that p21 is involved in C11-induced apoptosis. Although Bcl-2 has been implicated to interfere with an essential signaling molecule involved in the apoptosis pathway, its molecular mechanism and target molecule are poorly understood. To determine the effects of bcl-2 overexpression on apoptosis and to investigate whether BcI-2 interfers with the p53-independent p21 pathway, we transfected the bcl-2 expression vector into SK - Hep-1 cels. Overexpression of Bcl-2 prevented C11-induced apoptosis. Taken together, C11-induced apoptosis is regulated by p52-independent p21 pathway and bcl-2 may inhibit functional activity of p21, therebe may inhibit the C11-induced apoptosis.ptosis.

• Journal of Life Science
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• v.24 no.3
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• pp.242-251
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• 2014

The objective of this study was to isolate a photosensitizer from Pueraria thunbergiana leaves that induces apoptosis in SK-HEP-1 cells. Column chromatography and thin layer chromatography were used to isolate active compounds from extracts of P. thunbergiana leaves. The structures of the isolated compounds were determined by 1D-NMR, 2D-NMR, and FAB-mass spectroscopy. A substance, named M4-3, was purified from the leaves of P. thunbergiana using various chromatography methods, and the absorbance of the substance was measured. The absorbance was highest at 410 nm, suggesting that the M4-3 substance was a different compound from chlorophyll a and b, which absorb at 410, 502, 533, and 607 nm. Further analyses revealed that the M4-3 compound was a $13^2$-hydoxy pheophorbide, a methyl ester with a molecular weight of 662. M4-3 was identified as a derivative compound of pheophorbide, with a structure that magnesium comes away from the porphyrin ring. The results of the analysis of the cytotoxicity of the M4-3 substance against the SK-HEP-1 cells revealed that it inhibited rates of cell growth by 40% and 80% at a concentration of 0.04 ${\mu}M$ and 0.08 ${\mu}M$, respectively. The M4-3 compound was found to be a photosensitizer for cytotoxicity because it was appeared only in light condition as examining activity in different irradiation conditions (light condition and nonlight condition) under the same concentration. Analysis of morphological changes in the cells following cell death induced by exposure to the M4-3 substance reveled representative phenomena of apoptosis (nuclear condensation, vesicle formation, and fragmentation of DNA). The induction of apoptosis was attributed to the compound's photodynamic activity.

• 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.