• Journal of Nutrition and Health
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• v.26 no.4
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• pp.379-389
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• 1993

Several studies have shown that extracts from yellow-green vegetables reveal antitumor activities. In the present study we investigated the effect of phytol in order to elucidate the immunological mechanism of antitumor activity of this substance. The results obtained from the experiment as follows: 1) Phytol showed cytotoxic effect on sarcoma 180 cells in vitro. 2) When phytol was injected into the peritoneal cavity of mice transplanted with sarcoma 180 cells, the average survival time (24.0 days) tended to increase as compared with the nontreated control (19.2 days). 3) When sarcoma 180 cells were injected subcutaneously into the right groin of mice, and then phytol was injected into the peritoneal cavity, the tumor inhibition ratio was 33%. 4) The natural killer(NK) cell activity was significantly augmented by phytol in vitro and in vivo. Similar augmentations of NK cell activity were obtained with culture supernatants of phytol exposed spleen cells and peripheral blood mononuiclear cells. 5) Phytol on the macrophage from peritoneal cavity showed a higher effectiveness in vivo than in vitro. These results indicate that phytol shows the inhibitory effect for growth of sarcoma 180 cells in vitro, also it can augment macrophage and NK cell activities in vivo.

• Molecular Medicine Reports
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• v.20 no.4
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• pp.3301-3307
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• 2019

c-Myc is a characteristic oncogene with dual functions in cell proliferation and apoptosis. Since the overexpression of the c-Myc proto-oncogene is a common event in the development and growth of various human types of cancer, the present study investigated whether oncogenic c-Myc can alter natural killer (NK) cell-mediated immunity through the expression of associated genes, using PCR, western blotting and flow cytometry assays. Furthermore, whether c-Myc could influence the expression levels of natural killer group 2 member D (NKG2D) ligands, which are well known NK activation molecules, as well as NK cell-mediated immunity, was investigated. c-Myc was inhibited by 10058-F4 treatment and small interfering RNA transfection. Upregulation of c-Myc was achieved by transfection with a pCMV6-myc vector. The inhibition of c-Myc increased MHC class I polyeptide-related sequence B and UL16 binding protein 1 expressions among NKG2D ligands, and the overexpression of c-Myc suppressed the expression of all NKG2D ligands, except MHC class I polyeptide-related sequence A. Furthermore, the alteration of c-Myc activity altered the susceptibility of K562 cells to NK cells. These results suggested that the overexpression of c-Myc may contribute to the immune escape of cancer cells and cell proliferation. Combined treatment with NK-based cancer immunotherapy and inhibition of c-Myc may achieve improved therapeutic results.

• Journal of fish pathology
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• v.37 no.1
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• pp.111-122
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• 2024

This study assessed the impact of the toltrazuril derivative N-(4-(4-Fluorophenoxy)-3-methylphenyl) acetamide on natural cytotoxic cell (NCC) activity of olive flounder, Paralichthys olivaceus spleen. Five groups of fifteen olive flounder, comprising non-treatment and vehicle control groups, were randomly assigned. N-(4-(4-Fluorophenoxy)-3-methylphenyl) acetamide was injected intramuscularly at doses of 120, 150 and 200 mg/kg body weight; a total of ten injections were given over the course of 30 days. The NK activity of flounder splenic cells was evaluated against YAC-1, mouse lymphoma cells or HINAE cells with a choice of co-cultivation times of 4 or 18 hrs. In case of YAC-1 co-culture we observed a significant increase in cytotoxicity at a dose of 200 mg/kg, up to 3.06 times more than that of the control group. Only the trial with the 4 hrs co-culture produced a significant difference in the HINAE cell experiment; the experimental group at the 200 mg/kg dose exhibited the maximum cytotoxicity, demonstrating 2.3 times more cytotoxicity than the control group. Furthermore, the expression level of IL-12b was markedly induced in the group with 200 mg/kg, which was 6.62 times greater than that of the control group. In terms of the altered NK cell activity, the repeated high doses of N-(4-(4-Fluorophenoxy)-3-methylphenyl) acetamide can cause changes in the normal performance of immune function.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.255-261
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• 1999

The effect of biphenyl dimethyl dicarboxylate (PMC) on the cellular and nonspecific immunosuppressions by ketoconazole (KCZ) was investigated in ICR mice. PMC at a dose of 6 mg/kg was administered orally to mice daily for 14 consecutive days. KCZ was suspended in RPMI 1640 medium and orally administered at 160 mg/kg/day 2 hrs after the administration of PMC. Immune responses of the delayed-type hypersensitively (DTH) reaction to sheep red blood cells (SRBC), phagocytic activity and natural killer (NK) cell activity were evaluated. DTH reaction to SRBC was enhanced to normal level by the combination of PMC and KCZ, as compared with treatment of KCZ alone. In the combination of PMC and KCZ, as compared with treatment of KCZ alone, there were also significant increases in activities of natural killer (NK) cells and phagocytes along with circulating leukocytes. These findings indicate that PMC shows a significant restoration from the immunotoixc status induced by KCZ.

• BMB Reports
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• v.56 no.7
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• pp.398-403
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• 2023

Natural killer (NK) cells are an essential part of the innate immune system that helps control infections and tumors. Recent studies have shown that Vorinostat, a histone deacetylase (HDAC) inhibitor, can cause significant changes in gene expression and signaling pathways in NK cells. Since gene expression in eukaryotic cells is closely linked to the complex three-dimensional (3D) chromatin architecture, an integrative analysis of the transcriptome, histone profiling, chromatin accessibility, and 3D genome organization is needed to gain a more comprehensive understanding of how Vorinostat impacts transcription regulation of NK cells from a chromatin-based perspective. The results demonstrate that Vorinostat treatment reprograms the enhancer landscapes of the human NK-92 NK cell line while overall 3D genome organization remains largely stable. Moreover, we identified that the Vorinostat-induced RUNX3 acetylation is linked to the increased enhancer activity, leading to elevated expression of immune response-related genes via long-range enhancer-promoter chromatin interactions. In summary, these findings have important implications in the development of new therapies for cancer and immune-related diseases by shedding light on the mechanisms underlying Vorinostat's impact on transcriptional regulation in NK cells within the context of 3D enhancer network.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.247-251
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• 2005

Background: Natural killer (NK) cells are CD3 (-) CD14 (-) CD56 (+) lymphocytes. They play an important role in the body's innate immune response. They can induce spontaneous killing of cancer cells or virus-infected cells via the Fas/Fas ligand or the granzyme/perforin systems. The corticotropin-releasing hormone (CRH) is an important regulator for the body's stress response. It promotes proliferation and migration of various cancer cells through the CRH type 1 receptor under stress, and also inhibits NK or T cell activity. However, the relationship of CRH and NK cell migration to the target has not been confirmed. Herein, we study the effect of CRH on NK cell migration. Methods: We used the human NK cell line, NK-92MI, and tested the expression of CRH receptor type 1 on NK-92MI by RT-PCR. This was to examine the effect of CRH on tumor and NK cell migration, thus NK cells (NK-92MI) were incubated with or without CRH and then each CRH treated cell's migration ability compared to that of the CRH untreated group. Results: We confirmed that CRH receptor type 1 is expressed in NK-92MI. CRH can decrease NK cell migration in a time-/dose-dependent manner. Conclusion: These data suggest CRH can inhibit NK cell migration to target cells.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.91-99
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• 2015

Herpes simplex virus (HSV) is a common causative agent of genital ulceration and can lead to subsequent neurological disease in some cases. Here, using a genital infection model, we tested the efficacy of vinegar-processed flos of Daphne genkwa (vp-genkwa) to modulate vaginal inflammation caused by HSV-1 infection. Our data revealed that treatment with optimal doses of vp-genkwa after, but not before, HSV-1 infection provided enhanced resistance against HSV-1 infection, as corroborated by reduced mortality and clinical signs. Consistent with these results, treatment with vp-genkwa after HSV-1 infection reduced viral replication in the vaginal tract. Furthermore, somewhat intriguingly, treatment of vp-genkwa after HSV-1 infection increased the frequency and absolute number of $CD3^-NK1.1^+NKp46^+$ natural killer (NK) cells producing interferon (IFN)-${\gamma}$ and granyzme B, which indicates that vp-genkwa treatment induces the activation of NK cells. Supportively, secreted IFN-${\gamma}$ was detected at an increased level in vaginal lavages of mice treated with vp-genkwa after HSV-1 infection. These results indicate that enhanced resistance to HSV-1 infection by treatment with vp-genkwa is associated with NK cell activation. Therefore, our data provide a valuable insight into the use of vp-genkwa to control clinical severity in HSV infection through NK cell activation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.995-1000
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• 2004

This study was purposed to investigate the effect of Gamgung-tang(GGT) on immune responses induced by glucocorticoid in mice. GGT solution was treated by intraperitoneal injection for 7 days after glucocorticoid treatment(80㎎/㎏). And then B and T cell proliferation and cytolytic activity of natural killer(NK) cells were measured. There was 25% inhibition in B cell proliferation with treatment of glucocorticoid. However, B cell proliferation was not influenced by GGT treatment. T cell proliferation was also inhibited by 18.4% with treatment of glucocorticoid. On the other hand, T cell proliferation was increased dose-dependent manner in GGT treated group. Furthermore in purified T cell, the proliferation was furtherly increased than non-purified T cell. At concentration of 18㎎/mouse GGT, purified T cell proliferation was increase to above level of normal group. The cytotoxic activity of NK cell was decreased by 35.3% with treatment of glucocorticoid. In GGT treated group, the cytotoxic activity of NK cell was increased to the normal level. In purified NK cell, the cytolytic activity of NK cell was further increased than non-purifed NK cell. These results suggest that GGT may proliferate T cell that is suppressed by glucocorticoid, and activate NK cell activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7857-7861
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• 2014

Natural killer (NK) cells play an important role in anti-tumor immunity. Interleukin (IL)-18 is an immunoregulatory cytokine that induces potent NK cell-dependent anti-tumor responses when administrated with other cytokines. In this study, we explored the effects of combining IL-18 and IL-2 on NK cytotoxicity as well as expression levels of the NK cell receptor NKG2D in vitro. Freshly isolated PBMCs were incubated for 48 h with IL-18 and IL-2, then CD107a expression on $CD3^-CD56^+$ NK cells was determined by three-colour flow cytometry to evaluate the cytotoxicity of NK cells against human erythroleukemia K562 cells and human colon carcinoma HT29 cells. Flow cytometric analysis was also employed to determine NKG2D expression on NK cells. The combined use of IL-18 and IL-2 significantly increased CD107a expression on NK cells compared with using IL-18 or IL-2 alone, suggesting that the combination of these two cytokines exerted synergistic enhancement of NK cytotoxicity. IL-18 also enhanced NKG2D expression on NK cells when administered with IL-2. In addition, blockade of NKG2D signaling with NKG2D-blocking antibody attenuated the up-regulatory effect of combining IL-18 and IL-2 on NK cytolysis. Our data revealed that IL-18 synergized with IL-2 to dramatically enhance the cytolytic activity of human NK cells in a NKG2D-dependent manner. The results appear encouraging for the use of combined IL-18 and IL-2 in tumor immunotherapy.

• BMB Reports
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• v.54 no.1
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• pp.44-58
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• 2021

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.