• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.6
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• pp.1321-1325
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• 1999

The inhibitory effect of Ramaria botrytis on the mutagenicity in Salmonella assay and cytotoxicity on cancer cell were studied. Ramaria botrytis methanol extracts showed antimutagenic effects of 60~90% on B(a)P and AFB1 in S. typhimurium TA98 and TA100. These extracts showed 73~85% antimutagenicity on TA100 against MNNG. The methanol extracts with strong antimutagenic activities were further fractionated by ethylacetate and water, the ethylacetate fraction were found to be stronger antimutagen icity against MNNG than water fraction. Ramaria botrytis methanol extracts and ethylacetate fraction revealed the highest cytoxicity against HT 29 human colon adenocarcinoma cells in which cell growth was inhibited by 57~88% and 69~94% at 0.25~1.0mg/ml, respectively. These methanol extract and ethyl acetate fraction exhibited 53~79% and 66~87% inhibition against HepG2 human hepatocarcinoma cells, respectively. But water fraction showed only 10~24% inhibition. However, these extract and fractions did not show cytotoxic effect against human chang liver cells. From these results, it is considered that Ramaria botrytis has stronger antimutagenic and anticancer effects in vitro.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.297-302
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• 2003

Cnidii Rhizoma water extract (CRW) was tested for liver cancer chemopreventive potential by measuring the inhibition of phase I enzyme and benzo[a]pyrene-DNA adduct formation and induction of phase II detoxification enzymes. There was 17.0% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of 150 mg/ml CRW. At concentration of 30 mg/ml CRW, the binding of $[^3H]B[a]P$ metablites to DNA of NCTC-clone 1469 cell was inhibited by 33.3%. CRW was potent inducer of quinone reductase (QR) and glutathione S-transferase (GST) activities in cultured murine hepatoma Hepalc1c7 cells. However, hepatic glutathione (GSH) level was not influenced by CRW. These findings suggest that CRW has chemopreventive potential of liver cancer by inhibiting cytochrome P450 1A1 activity and benzo[a]pyrene-DNA adduct formation and inducing QR and GST activities.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2375-2380
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• 2014

In the present investigation, a series of some novel 1,3-diaryl/heteroarylprop-2-en-1-one derivatives (3a-j) have been synthesized and evaluated for their in vitro cytotoxicity against three cancer cell lines, two hepatocarcinoma cell lines HUH-7, Hep-3b and one leukemia cancer cell line MOLT-4. Based on these results, structure-activity relationship (SAR) was studied on modification of $R^1$ and $R^2$ to identify the compound with maximum potency. Amongst the compounds, 3b and 3d strongly inhibited the growth of Hep-3b and MOLT-4 cells with $IC_{50}$ value of 3.39 and $3.63{\mu}M$ respectively. The results obtained from the inhibitory study had further been supported by the reactive oxygen species (ROS) measurement using flow cytometry in MOLT-4 cells. These observations collectively reveal that compounds comprising 1,3-diarylprop-2-en-1-one framework with pyrazole ring at position-3 and heteroaryl/aryl substituents at position-1 can be used as promising anticancer agents.

• BMB Reports
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• v.46 no.12
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• pp.611-616
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• 2013

Luteolin-7-O-glucoside (LUT7G), a flavone subclass of flavonoids, has been found to increase anti-oxidant and anti-inflammatory activity, as well as cytotoxic effects. However, the mechanism of how LUT7G induces apoptosis and regulates cell cycles remains poorly understood. In this study, we examined the effects of LUT7G on the growth inhibition of tumors, cell cycle arrest, induction of ROS generation, and the involved signaling pathway in human hepatocarcinoma HepG2 cells. The proliferation of HepG2 cells was decreased by LUT7G in a dose-dependent manner. The growth inhibition was due primarily to the G2/M phase arrest and ROS generation. Moreover, the phosphorylation of JNK was increased by LUT7G. These results suggest that the anti-proliferative effect of LUT7G on HepG2 is associated with G2/M phase cell cycle arrest by JNK activation.

• Archives of Pharmacal Research
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• v.29 no.2
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• pp.140-144
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• 2006

Four xanthones were isolated from mycelia of Emericella variecolor, an endophytic fungus isolated from the leaves of Croton oblongifolius. Their structures were elucidated by spectroscopic analysis to be shamixanthone, 14-methoxytajixanthone-25-acetate, tajixanthone methanoate, and tajixanthone hydrate. All compounds were tested for cytotoxic activity against various human tumor cell lines including gastric carcinoma, colon carcinoma, breast carcinoma, human hepatocarcinoma, and lung carcinoma. The antitumor activities of these xanthones were compared with that of doxorubicin hydrochloride, a chemotherapeutic substance. All of them showed moderate activities and were selective against gastric carcinoma, colon carcinoma, and breast carcinoma. Only tajixanthone hydrate exhibited moderate activity against all cancer cell lines. Furthermore, under the test conditions it was found that 14-methoxytajixanthone-25-acetate and tajixanthone hydrate are almost as active as doxorubicin hydrochloride against gastric carcinoma (KATO3) and breast carcinoma (BT474).

• Korean Journal of Food Science and Technology
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• v.44 no.5
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• pp.638-642
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• 2012

Human pathogenic viruses such as hepatitis A and E virus (HAV and HEV), which lead to acute liver failure and death, are foodborne pathogens associated with the consumption of virus-contaminated meats, filter-feeding bivalves, fruits, and salads. Two of the three swine farms examined in this study had HAV and HEV positive stool samples in a nested RT-PCR assay. The use of the immunomagnetic separation (IMS) facilitated the separation of HAV through interactions between the ligand on the virion surface and the antibody from the swine feces containing both HAV and HEV. The nested RT-PCR analysis was performed for the detection of HAV obtained from hepatocarcinoma cell line (PLC/PRF/5) contaminated with eluent fraction of IMS. This indicated that IMS has the potential to simultaneously isolate and concentrate target viruses by changing antibodies linked on the magnetic beads.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1825-1831
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• 2004

Phellinus linteus is known as a medicinal mushroom, which has the pharmaceutical activity on tumors and inflammatory diseases in traditional Oriental medicine. However, despite extensive pharmacological studies on P. linteus, the liquor of fermentation using mycelium of P. linteus(LFMP) has not been investigated. In the present study, it was examined the effect of the evaporating extract from LFMP(E-LFMP) on the expression of inflammatory proteins and the generation of reactive oxygen species in human hepatocarcinoma HepG2 cells. E-LFMP inhibited acetaldehyde-induced morphological change in HepG2 cells. Also, E-LFMP inhibits expression of inflammatory proteins including cyclooxygenase(COX)-1 and COX-2 through suppressing nuclear translocation of nuclear factor κB(NF-κB) and degradation of inhibitory κBα(IκBα). In addition, E-LFMP inhibits generation of reactive oxygen species(ROS) by hydrogen peroxide(H₂O₂) in HepG2 cells. These results suggest that LFMP has the pharmaceutical, especially anti-inflammatory, activity similar to P. linteus mushroom.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.599-607
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• 2018

Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration-(>$50{\mu}M$) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to $500{\mu}M$. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at$25{\mu}M$. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.993-1001
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• 2016

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.