• YAKHAK HOEJI
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• v.41 no.5
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• pp.629-637
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• 1997

Tumor necrosis factor-${alpha}$ (TNF) induced a cytotoxic response in ME-180 cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of mitogenic stimuli : increased c-fos, c-jun and jun-B expression. Depletion of protein kinase C (PKC) by exposure of ME-180 cells to 100ng/ml phorbol myristate acetate (PMA) for 24hours almost completely abolished TNF-mediated increase in these signals, indicating that a PKC-dependent pathway is involved in TNF-mediated increases in the expression of c-fos, c-jun and jun-B. Characteristics of TNF receptors after exposure to 100ng/ml PMA or 24hours were not altered, suggesting that diminished induction of these oncogenes by TNF after PMA treatment is not due to any changes at the receptor level. To examine whether a PKC-dependent pathway is involved in TNF-mediated cytotoxicity in ME-180 cells, cytotoxicity was measured after depletion of PKC. No apparent changes in cytototoxicity after PKC depletion suggest that a PKC-dependent pathway is not involved in TNF-mediated cytotoxicity. Furthermore, results from cytotoxicity tests after exposure to staurosporine (PKC inhibitor) did not show any changes in the TNF-mediated cytotoxicity, confirming that a PKC-dependent pathway is not involved in this process. These data indicate that 1) TNF induces expression of c-fos, c-jun and jun-B oncogenes via a PKC-dependent pathway and 2) PKC-dependent expression of these three oncogenes by TNF may not be involved in TNF-mediated cytotoxicity in ME-180 cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.1 s.32
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• pp.66-79
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• 2007

Objectives : This study was carried out to evaluate anti-tummor effect about apoptosis of Cheongyulsodok-Eum (CSE) Results : 1. Anti-tumor(HL-60 cells) effects of CSE water extracts(Exts) were more effective in high density.($IC_{50:}:572$ ${\mu}g/ml$) 2. The generation of $O_2\;^-$ in HL-60 cells were according to the concentration of CSE water Exts, specially more effective on 100 ${\mu}g/ml$ and 1000 ${\mu}g/ml$ concentration. 3. The SOD activities in HL-60 cells were in proportion as cytotoxicity against HL-60 cells of CSE water Exts. 4. The GPx activities in HL-60 cells were in proportion as cytotoxicity against HL-60 cells of CSE water Exts(more effective on 100 ${\mu}g/ml$ and 1000 ${\mu}g/ml$ concentration), but the catalase activities in HL-60 cells were not effective. 5. DPPH radical scavenging activity of CSE water Exts was effective.(3 ${\mu}g/ml:31.2{\pm}5.2$ %, 10 ${\mu}g/ml:49.6{\pm}7.3$ %, 30 ${\mu}g/ml:35.8{\pm}5.7$ % 100 ${\mu}g/ml:42.3{\pm}6.4$ %) 6. The results of cytotoxicity against HL-60 cells of CSE were as follows. 1) In hexane fraction, the cytotoxicity against HL-60 cells($IC_{50:}:592$ ${\mu}g/ml$) was more effective than against NIH3T3 cells. 2) In ethyl acetate fraction, the cytotoxicity against HL-60 cells was not effective. 3) In butanol fraction, the cytotoxicity against HL-60 cell($IC_{50:}:306$ ${\mu}g/ml$) was more effective than against NIH3T3 cells. 4) In $H_2O$ fraction, the cytotoxicity against HL-60 cells was not effective. Conclusion : These result suggest that CSE has antioxidative effects and anti-tumor effects by apoptosis of free radical($O_2\;^-$) activity, especially butanol and hexane fraction from water extract has more effective in anti-twnor effects.

• Journal of Environmental Health Sciences
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• v.27 no.2
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• pp.82-91
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• 2001

This study was carried out to elucidate the protective effect of zinc chloride(ZnCl$_2$) and its mechanism against the immuno-cytotoxicity of methylmercury chloide($CH_3$HgCl). This study was observed in the culture of EMT-6 cells which are originated from mammary adenocarcinoma of Balb/c mouse. Cytotoxicity of metals was measured by cell viability and NO$_2$$^{[-10]}$ , and mitochondrial function was evaluated by adenosine triphosohate (ATP) production. $CH_3$HgCl significantly decreased the sythesis of nitric oxide(NO), ATP and glutathione(GSH) in a dose-dependent manner. ZnCl$_2$ significantly increased the synthesis of GSH in a dose-dependent manner, but synthesis of NO and ATP were not changed. The immuno-cytotoxicity of $CH_3$HgCl was not fully protected when combined addition of ZnCl$_2$, whereas ZnCl$_2$ prior to addition of $CH_3$HgCl completly protected the Hg-induced immuno-cytotoxicity. Similarly, intracellular accumulation of mercury significantly decreased by ZnCl$_2$. Degree of diminution of intracellular mercury was larger in ZnCl$_2$ prior to addition of $CH_3$HgCl than in combined addition of ZnCl$_2$ and $CH_3$HgCl.. Dithiothreitol(DTT) or buthionine sulfoximine(BSO) addition at 50$\mu$M or less, which was not toxic to the cells, did not affect synthesis of NO and ATP. DTT increased intracellular GSH level and DTT pretreatment protected toxicity induced by $CH_3$HgCl as shown complete recover in the NO and ATP values. BSO decreased intracellular GSH level and BSO pretreatment exaggerated toxicity induced by $CH_3$HgCl as shown synergistic reduction in the NO and ATP values. These results indicated that the protective effects of zinc against immuno-cytotoxicity of methylmercury associated with increasing cellular level of GSH. Increased intracellular GSH transports methylmercury to out of cells. In accordance with intracellular level of mercury decreased, immuno-cytotoxicity of methylmercury decreased. These result also suggest that the protective mechanism of zinc against the mercury toxicity would be exerted in the immune system in vivo.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.4
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• pp.363-370
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• 2021

This study was conducted to evaluate the dermal cytotoxicity of lead acetate (LA) and other heavy metal compounds, and the protective effect of Lespedeza bicolor (LB) extract on LA-induced cytotoxicity in cultured B16-/F10 melanoma cells. The study evaluated the antioxidative effects of LB due to its electron-donating ability (EDA), inhibitory effects on melanization and improving cell viability. LA significantly decreased cell viability in a dose-dependent manner, and the XTT₅₀ value was determined at 52.7 µM in the studied cultures. Based on the Borenfreund and Puerner's toxicity criteria, LA was estimated to be highly cytotoxic. LA-induced cytotoxicity and cell damage was reversed by the antioxidant activity of kaempferol (KAE), thereby remarkably improving cell viability. A study of the protective effects of the LB extract on LA-induced cytotoxicity showed that the LB extract remarkably increased cell viability in the LA-treated group, and also inhibited the EDA and the total amount of melanin. The above results suggest oxidative stress-mediated cytotoxicity of LA. In the study, LB extract effectively prevented LA-induced cytotoxicity via its antioxidative activity and inhibition of melanization. In conclusion, natural resources like LB extracts may be useful agents for the prevention of oxidative stress-mediated cytotoxicity and melanization by heavy metallic compounds such as LA.

• Natural Product Sciences
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• v.6 no.4
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• pp.165-169
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• 2000

In vitro cytotoxic activities of cisplatin combined with Chungpesagan-tang or puerarin, which were treated with or without human intestinal bacteria, were measured. When cisplatin was combined with Chungpesagan-tang and its ingredient treated without intestinal bacteria, they did not affect the in vitro cytotoxicity of cisplatin against tumor cell lines. However, when cisplatin was combined with intestinal bacteria-treated Chungpesagan-tang and its ingredients, the cytotoxicities against SNU C4, L1210, A549 and P388 tumor cell lines were synergistically increased. Puerarin, which was isolated from Puerariae Radix, did not show in vitro cytotoxicity. However, its metabolite, daidzein, showed potent cytotoxicity against tumor cell lines and was synergistic by the combined usage of cisplatin. These results suggest that natural glycosides are not only prodrugs which can be transformed to active compounds by intestinal microflora, but the combined usage of cisplatin with natural components, such as daidzein, and herbal medicinal polyprescriptions, such as Chungpesagan-tang, may be a new method for prevention and minimization of the toxicity of cisplatin.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.820-823
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• 2002

The diethylet er fraction from the leaves extract of Ligularia fischeri var. spiciformis (Compositae) was subjected to silica gel column chromatography and yielded three new terpenoids named spiciformisin a (1), spiciformisin b (3), and monocyclosqualene (2). Acyclic diterpenes, spiciformisin a and -b, were established as 3,7,11,15-tetramethyl-1,3(20)-hexadecadiene and 3,7,11,15-tetramethyl-1,3,6,10,14-hexadecapentaene (IUPAC), respectively. A monocyclic triterpene, monocyclosqualene, were determined as [3,8,12,16,16-pentamethyl-(3,7,11,15-hexadecatetraenyl)]-3,3,5-trimethyl-1-cyclohexene. The structures were determined on the basis of NMR and MS analysis. Spiciformicin b showed potent cytotoxicity ($IC_{50},{\;}<9.7{;\}{\mu\textrm{g}}/ml$ against HL-60) in contrast to no cytotoxicity ($IC_{50},{\;}>200{\;}}{\mu\textrm{g}}/ml against HL-60 cells) of spiciformicin a with a cis-conjugated dienyl diexomethylene.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.359-366
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• 2001

We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,3-dichloropropane (DCP) as a leaving group. A new series of [Pt(cis- DACH)(DCP)](PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. The new platinum complex has demonstrated high efficacy in the cytotoxicity against MKN-45/P, MKN-45/ADM and MKN-45/CDDP cell-lines. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined by MTT assay, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new, clinically available anticancer chemotherapeutic agents.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.1
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• pp.55-64
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• 2006

Objective : The purpose of this study was to investigate effect of Gungguitakli-San(GTS) on the anti-tumor, immunocytes. Methods : This study estimated the proliferation of L1210 and S-180 cell lines, mouse splenocytes and thymocytes in vitro, and estimated the proliferation of L1210 cell, S-180 cell, thymocytes and splenocytes and body weight in S-180 cells-transplanted mice. The cytotoxicity and proliferation of cells were tested using a colorimetric tetrazoliun assay(M1T assay). Results : The results of this study were obtained as follow ; 1. GTS was significantly increased in the proliferation of thymocytes and splenocytes In vitro. 2. GTS was significantly showed cytotoxicity on the L1210 cell lines and 8-180 cell lines in vitro. 3. GTS was significantly showed cytotoxicity on the L1210 cell lines in vivo. 4. GTS was significantly increased in the weight of mice and decreased weight of sarcoma, in S-180 cells transplanted mice. 5. GTS was significantly increased in the period of survive, in S-180 cells transplanted mice. Conclusions : The author thought that GTS had action of anti-cancer by becoming immunocytes activity and by cytotoxicity of cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.6
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• pp.1177-1182
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• 1998

The antimutagenic and cancer cell growth inhibitory effects of woorimil contained herb and seaweed powders were examined. While woorimil itself showed only 40% antimutagenic effect on S. typhymurium TA98 against 4NQO(0.15 g/plate), water extracts of mountain herbs and seweeds including Comfrey, wormwood, Kale, Angelica utilis and pine leaves showed 80~90% antimutagenicity. On the other hand, these extracts along with woorimil showed 68 to 80% antimutagenic activities. Low antimutagenic activities of less than 50% were shown when these extracts were tested on TA98 against Trp P 1(0.5 g/plate), but high antimutagenic activities of 80~93.3% were shown on TA100. Water extracts of Capsella bursa pastoris and Allium grayi exhibited 60~80% of the activites in cytotoxicity tests of woorimil water extracts(0.5mg/ml) on human lung carcinoma cell. A549 showed 10% cell growth inhibitory effect. When mixed with Comfrey and Angelica utilis extracts, it showed 23~25% inhibition and other extracts showed only 12~23% inhibition. Cytotoxicity test of woorimil extracts on human liver cancer cell Hep3B revealed 20% inhibition. The additions of pine needle extracts, Angelica utilis and Comfrey showed 33%, 29% and 25% inhibition, respectively. But other extracts showed only 20% inhibition.

• Korean Journal of Environmental Biology
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• v.30 no.3
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• pp.157-163
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• 2012

Oxidative stress has been reported to be one of causes of neuritis. This study examined antioxidative activities of methanol extracts of six amphibian species known to be medicinal animals (Rana catesbeiana, R. coreana, R. rugosa, R. dybowskii, R. nigromaculata, and Hyla japonica) and investigated their effects of inhibiting nitric oxide (NO) production and cytotoxicity on the murine macrophage RAW264.7 cells. As inflammation is closely associated with reactive oxygen species, assays on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, xanthine oxidase inhibitory activity, superoxide anion radical scavenging activity and NO scavenging activity of the extracts of the six species were performed to investigate their antioxidative activity. The results obtained were as follows; All extracts showed antioxidative activity, and the activity of R. dybowskii was the highest in comparison among those. Anti-inflammatory effects of the extracts were also examined, the five extracts except that of R. rugosa did not show cytotoxicity for RAW264.7 cells at the maximal concentration ($1,000{\mu}g\;mL^{-1}$). Selectivity index, meaning NO scavenging activity compared to cytotoxicity, showed the highest level in the extract of R. dybowskii. These results will be very useful basic data for future studies on prevention and treatment of human diseases to understand the biological roles of amphibian extracts throughout the antioxidative or anti-inflammatory pathways.