• IMMUNE NETWORK
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• v.12 no.6
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• pp.240-246
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• 2012

Natural killer (NK) cells play a pivotal role in early surveillance against virus infection and cellular transformation, and are also implicated in the control of inflammatory response through their effector functions of direct lysis of target cells and cytokine secretion. NK cell activation toward target cell is determined by the net balance of signals transmitted from diverse activating and inhibitory receptors. A distinct feature of NK cell activation is that stimulation of resting NK cells with single activating receptor on its own cannot mount natural cytotoxicity. Instead, specific pairs of co-activation receptors are required to unleash NK cell activation via synergy- dependent mechanism. Because each co-activation receptor uses distinct signaling modules, NK cell synergy relies on the integration of such disparate signals. This explains why the study of the mechanism underlying NK cell synergy is important and necessary. Recent studies revealed that NK cell synergy depends on the integration of complementary signals converged at a critical checkpoint element but not on simple amplification of the individual signaling to overcome intrinsic activation threshold. This review focuses on the signaling events during NK cells activation and recent advances in the study of NK cell synergy.

• Biomolecules & Therapeutics
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• v.14 no.3
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• pp.148-151
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• 2006

We have previously reported that 2.4 kb of L-plastin promoter (LP) could regulate the expression of adenoviral vector (AV) exogenous genes in a tumor cell specific manner. In the present study, we tested if the replication competent AdLPE1A vector results in a direct cytotoxic effect in hepatocelluar carcinoma (HCC) cells. In vitro cytotoxicity tests were carried out with replication-competent (AdLPE1A) and -incompetent (AdLPCD) LP-driven vectors. AdLPE1A is an AV in which LP was inserted 5' to the E1A and E1B genes. The AdLPCD vector contains LP and the E. coli cytosine deaminase (CD) gene in transcription unit. Exposure of cells to AdLPE1A generated a significant cytotoxic effect as compared to the control. Almost 90% of the cell had manifested the characteristic cytopatic effect on day 9 after infection of cells with 10 MOI of AdLPE1A. On the other hand, almost 35% of the cells were left when the cells had been treated with 100 MOI of AdLPCD together with 5-FC on day 9 when compared with the cells which had never been exposed neither 5-FC nor AdLPCD. These results showed that the replication competent AdLPE1A vector could kill the HepG2 cells directly by the oncolytic effect of the virus. The replication competent AV vector carrying viral E1A generated greater cytotoxic effect than the replication incompetent AV, which contains the CD prodrug activation transcription unit without E1A, in HepG2 cells.

• The Journal of the Korean Society for Microbiology
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• v.21 no.1
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• pp.163-170
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• 1986

Balb/c mouse spleen cells in vitro sensitized against ICR spleen cells were cultured in conditioned media(CM). The CM was produced by ICR spleen cells stimulated with Concanavalin-A(Con-A), and sensitized lymphoid cells were grown in CM. ICR mouse spleen cells were appeared to be a good generator of IL-2. Optimal growth was seen in growth medium containing 20% fetal calf serum. and 25% CM. When cultures were initiated at 1, 5, $10{\times}10^4\;cells/ml$, the cells were increased in numbers by about 20, 13, 5-fold, respectively, every 9 days. Such growth pattern was sustained for about 4-6 weeks and thereafter the cell growth was diminished gradually. Direct immunofluorescence indicated that 93% of the lymphoid cells grown in CM(for 10 days) expressed Thyl surface antigen. And the cells grown in CM were cytotoxic to the sesitizing ICR mouse spleen cells though cytotoxicity level was not high. According to these results, the cells grown in CM were considered to be cytotoxic T lymphocytes. The lymphoid cells grown for 20 days were nearly unresponsive to Con-A and therefore dependent only IL-2 to be used for IL-2 assay.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.48-59
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• 2005

Objectives : The aim of the study was to evaluate the effect of WS on HepG2 cell cycle and expression of related genes. Methods : The MTT assay, Cell counting analysis, $[^3H]-Thymidine$ Incorporation Assay, Flow cytometric analysis, Quantitative RT-PCR were studied. Results : WS inhibited HepG2 cell proliferation in low concentration$(1-10\;{\mu]g/ml)$ which did not cause direct cytotoxicity, with dose-dependant manner. WS in-hibited DNA synthesis as well. Flow cytometric analysis on the HepG2 cell showed G2/M phase arrest. Conclusion : These results suggest that WS inhibits HepG2 cell proliferation not by the gene regulation but by G2/M phase arrest in the cell cycle. Thus further studies on the effect of WS in G2/M phase regulation are thought to be needed.

• Molecules and Cells
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• v.22 no.1
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• pp.21-29
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• 2006

The aim of this study was to determine if hydrogen peroxide ($H_2O_2$) generated by glucose oxidase (GO) induces apoptosis or necrosis of BJAB cells and which radical is the direct mediator of cell death. We found that GO produced $H_2O_2$ continuously in low concentrations, similar to in vivo conditions, and decreased proliferation and cell viability in a dose-dependent manner. The GO-mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the cells after H33342/Annexin V/propidium iodide staining. Decreases of mitochondrial membrane potential and intracellular glutathione level were found to be critical events in the $H_2O_2$-mediated apoptosis. Additional experiments revealed that $H_2O_2$ exerted its apoptotic action through the formation of hydroxyl radicals via the Fenton rather than the Haber-Weiss reaction. Moreover, intracellular redox-active iron, but not copper, participated in the $H_2O_2$-mediated apoptosis.

• Proceedings of the KOSOMBE Conference
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• v.1996 no.05
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• pp.133-136
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• 1996

We investigated how hydroxyapatite (HA) coating onto a porous super stainless steel (S.S.S, 22Cr-20Ni-6Mo-0.25N) affects bone ingrowth in a dog transcortical femoral model. Implants were histologically evaluated after 4 and 48 weeks of implantation, and the bone bonding strength at the bone/implant interface was examined by employing the pull-out test. The direct osseous tissue bonding onto the HA-coated S.S.S was observed, but the uncoated stainless steels had thin fibrous tissue layers. The mean interface strength of the HA-coated S.S.S was 1.5 and 2.5 times greater than those of the S.S.S and the 316L SS after one year of implantation, respectively. In preliminary studies, no toxic responce was observed from a cytotoxicity test of the S.S.S, having similar corrosion resistance to titanium. Our results suggest that early osteoconductive nature of HA coating may induce long term osteointegration for a bioinert substrate.

• Korean journal of food and cookery science
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• v.21 no.6 s.90
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• pp.759-768
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• 2005

This study was performed to determine the antioxidative effect of the hexane, dichloromethane, ethylacetate, butanol and water fractions of Ganoderma lucidum extracts on the inhibition of malondialdehyde(MDA) and bovine serum albumin(BSA) conjugation reaction, the inhibition of lipid peroxidation and the scavenging effect on 1,1-diphenyl-2-picryl-hydrazyl(DPPH) radical, the antimutagenic capacity as measured by the Ames test and the inhibitory effect on cancer cell. Ganoderma lucidum is believed to have possible antioxidative capacities, although the results have varied according to the assay method. The most effective antioxidative capacity was inhibition of lipid peroxidation. Among the five fractions, water fraction showed strong inhibition rates on MDA & BSA conjugation reaction, and ethylacetate fractions showed the most effective inhibition rate on lipid peroxidation and scavenging effect on DPPH radical. The indirect and direct antimutagenic effects of ethanol extracts of Ganoderma lucidum were examined by Ames test using Salmonella typhimurium TA98 and TA100. Among the samples, the water fraction did not have any antimutagenic effect. The inhibition rates on mutagenicity in the presence of 2.5 mg/plate were nearly $100\%$ for Salmonella typhimurium TA98 and TA100 except the hexane fraction of the direct mutagenicity mediated by 2-Nitrofluorene in Salmonella typimurium TA98($64.69\%$). Under the 2.5 mg/plate concentration, the inhibitory effects of hexane and dichloromethane fraction were superior to that of the other fractions on the direct mutagenicity for Salmonella typhimurium TA100 and indirect mutagenicity for Salmonella typhimurium TA98 and TA100. The inhibitory effect of Ganoderma lucidum extracts on cell proliferation in HeLa and MCF-7 was investigated by U test. The dichloromethane fraction showed highly antiproliferative effect in HeLa and MCF-7($IC_{50}$: 0.122 mg/mL, 0.272 mg/mL, respectively) cells while the water faction had a weak inhibitory effect($IC_{50}$: 0.691 mg/mL, 10.919 mg/mL respectively). These results suggest that Ganoderma lucidum may have antioxidative, antimutagenic and anticancer capacities and may be a candidate of the prevention and dietetic treatment of chronic diseases and the development of antioxidative, antimutagenic and anticancer functional food.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.5
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• pp.515-520
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• 2007

This study was peformed to determine the antioxidative, antimutagenic and cytotoxic effects of the natural seasoning using Lentinus edodes powder (NSLP) by DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical donating method, Ames test, and cytotoxicity, respectively. The scavenging effect on DPPH radical in ethyl acetate fraction of NSLP showed $155{\mu}g\;of\;RC_{50}$. The direct antimutagenic effects of ethanol extract and its solvent fractions of NSLP were examined by Ames test using Salmonella Typhimurium TA98 and TA100. In the Ames test, ethanol extract of NSLP alone did not exhibit any mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitroso guanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). Ethyl acetate fraction of NSLP ($200{\mu}g/plate$) showed approximately 82% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 84% and 80% inhibitions were observed on the mutagenesis induced by 4NQO and MNNG against TA100 strain. In anticancer effects of ethanol extract and its solvent fractions of NSLP against cancer cell lines including human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), human hepatocellular carcinoma (Hep3B), human cervical adenocarcinoma (HeLa) and human gastric carcinoma (AGS) were investigated. The treatment of 1 mg/mL ethyl acetate fraction of NSLP showed strong cytotoxicity of 56.7%, 84.9%, 64.6%, 85.1% and 71.5% against A549, MCF-7, Hep3B, HeLa and AGS, respectively. In contrast 1 mg/mL treatment of NSLP extract and its solvent fractions had only $4{\sim}40%$ cytotoxicity on human transfomed primary embryonal kidney cell (293). From this result, it is suggested that NSLP is believed to have possible antioxidative, antimutagenic and anticancer capacities.

• Korean Journal of Food Science and Technology
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• v.30 no.6
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• pp.1470-1475
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• 1998

Two kinds of Korean rice-wine (Yakju) with different process and ingredients, and Japanese rice-wine (Sake) were chosen for this study, and throughly dried and solubilized in water or cell culture medium. In vitro cytotoxicity assays of the solubilized wine solids exhibited that maximum dilution factors for inhibition of B 16BL6 mouse melanoma cell growth were 16X for herbal medicine-added rice-wine (Korean rice-wine I) and typical Korean rice-wine (Korean rice-wine II), and 8X for Japanese rice-wine. Their cytotoxic effects on HRT18 human colon adenocarcinoma cells were even lower than those on B16BL6 cells. The morphology of the tumor cells were changed by addition of the solubilized wine solids. Inhibitory effect of the rice-wine on in vivo tumor growth and metastasis were monitored after implantation of B16BL6 cells into C57BL/6 mice with daily feeding the solubilized wine solids. Compared to non-fed control groups, B16BL6 tumor growth and metastasis to lung were clearly inhibited by feeding the wine solids, in order of Korean rice-wine I > Korean rice-wine II > Japanese rice-wine. The data of in vitro cytotoxicity and the cell shape changes indicate that the inhibitory effect of tumor progression may be attributed to tumor cell differentiation or immune stimulation induced by certain components in the rice-wine, rather than direct cytotoxicity of the components.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.3 no.1
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• pp.85-98
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• 1997

Oriental medicine as a candidate for effective cancer treatment recently gain positive concerns in fields of therapeutic oncology. that is why some herbal medicines have been empirically safer in toxicity than anticancer drugs used in western medicine, and to show excellent therapeutic efficacy in human trial. Thus, these effects by clinically applied-herbs have not yet fully demonstrated in experimental tumor model. This study was initiated to evaluate the antitumor effect of Insambaekhaptang as candidate of antitumor-herbal agent against B16 melanoma metastasized into C57BL/6 mice lung. In experiment to test whether Insambaekhaptang can directly kill cancer cells in vitro or not, Insambaekhaptang showed direct killing action in concentration or higher against B16 melanoma cells using MTT assay, and showed lower IC50. Another experiment to know whether Insambaekhaptang can inhibit growth and metastasis of cancer cell or not, Insambaekhaptang significantly inhibited Solid tumor by intraperiperal injected-melanoma and lung metastasis induced by intravenous injected-melanoma in inbred C57BL/6 mice. When quantitative survival time increasing, we could obtain results that increased 113% in treated by Insambaekhaptang. These results show that Insambaekhaptang can inhibit growth of B16 melanoma cells through various biological mechanisms.