• Biomedical Science Letters
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• v.29 no.4
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• pp.371-375
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• 2023

Natural killer (NK) cells are innate immune cells and play important roles as the first immune cells to recognize and kill cancer. In patients with advanced and terminal cancer, NK cells are often inactivated, suggesting that NK cells may play important roles in cancer treatment. In particular, the proportion of NK cells among immune cells infiltrating tumor tissues is often low, which suggests that NK cells do not survive in tumor microenvironment (TME). In order to overcome these hurdles of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic activity of NK cells. We applied Vemurafenib to NK cells and measured the degree of NK cell proliferation and functional activation. We obtained unexpected results of increased NK cell numbers and anti-tumor activity after Vemurafenib treatment. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Vemurafenib is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.165-170
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• 2017

Cordyceps bassiana is one of Cordyceps species with anti-oxidative, anti-cancer, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic, and anti-nociceptive activities. This mushroom has recently demonstrated to have an ability to reduce 2,4-dinitrofluorobenzene-induced atopic dermatitis symptoms in NC/Nga mice. In this study, we further examined phytochemical properties of this mushroom by column chromatography and HPLC analysis. By chromatographic separation and spectroscopic analysis, 8 compounds, such as 1,9-dimethylguanine (1), adenosine (2), uridine (3), nicotinamide (4), 3-methyluracil (5), 1,7-dimethylxanthine (6), nudifloric acid (7), and mannitol (8) were identified from 6 different fractions and 4 more subfractions. Through evaluation of their anti-inflammatory activities using reporter gene assay and mRNA analysis, compound 1 was found to block luciferase activity induced by $NF-{\kappa}B$ and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor $(TNF)-{\alpha}$. Therefore, our data strongly suggests that compound 1 acts as one of major principles in Cordyceps bassiana with anti-inflammatory and anti-atopic dermatitis activities.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.205-212
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• 2009

Antitumor activity of Korean mistletoe extract (KM-110) and European commercial mistletoe preparation (Helixor) was investigated. KM-110 showed the cytotoxic effect that it is high for various tumor cell lines and normal splenocytes in comparison with Helixor. Administration of two mistletoe extracts ($100{\mu}g$) to mice did not show any significant changes on the level of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvate transaminase (GTP), blood creatinine (CRE) and blood urea nitrogen (BUN) in sera. The culture supernatant of macrophages stimulated with KM-110 inhibited effectively tumor growth whereas Helixor had little effect. Administration of KM-110 or Helixor resulted in a effective inhibition of lung metastasis after the i.v. inoculation of colon 26-M3.1 lung carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphomas. In all cases, the mice treated with KM-110 showed more effective anti-tumor metastatic activity than the mice of Helixor. These results suggest that Korean mistletoe extracts, KM-110 might be used as an alternative methods having antitumor activity like European mistletoe preparation, Helixor.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3857-3862
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• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

• Korean Journal of Pharmacognosy
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• v.36 no.4 s.143
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• pp.332-337
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• 2005

We here demonstrate the evidence of increased anti-tumor and immunostimulating activities of crude extracts (GAL) from Galium. aparine L. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma cells, prophylactically intravenous (i.v) administration of GAL significantly inhibited lung metastasis in a dose-dependant manner. In an in vitro cytotoxicity analysis, GAL at the concentration up to $500\;{\mu}g/ml$ did not affect the growth of B16-BL6 melanoma cells. In contrast, GAL showed the enhancement of splenocyte proliferating activity in a dose-dependent manner. Peritoneal macrophages stimulated with GAL produced various cytokines such as $1L-1{\beta},\;TNF-{\alpha},\;IFN-{\gamma}$ and IL-12. These data suggest that GAL has an antitumor activity to inhibit tumor metastasis, and its antitumor effects is associated with activation of nonspecific immnune related cells.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.8 no.1
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• pp.103-125
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• 2002

This experimental study was carried out to evaluate the anti-tumor and the immunomodulatory effects of Jiaweicitaowan(加未慈桃丸) against cancer. The in vitro anti-tumor effects were evaluated by MTT assay. The cytotoxicity, extension of survival days, the effect of inhibition solid tumor which was induced sarcoma 180, and the changes of body weight were evaluated for in vivo effects of anti-tumor. To evaluate the immunomodulatory effects of Jiawei- citaowan(加未慈桃丸), delayed type hypersensitivity, hemagglutinin, hemolysin titers for humoral immune response, rosette forming cells for cell-mediated immune response, natural killer cell activity, proliferation of lymphocyte, productivty of Interleukin-2, and carbon clearance were measured with methotrexate treated mice. The results were as follows; 1. In the case of existence ability of tumor cell, IC50 had an anti-tumor ativity resulted 2.52mg/ml to SNU-C4. 0.41mg/ml to SNU-396, resulted to 0.09mg/mlSNU-1. 2. The groups of Jiaweicitaowan(加未慈桃丸) 10mg/ml, 20mg/kg had no body weight loss. reduction in intake of water and feed, so these had no toxicity. 3. In the case of the effect of extention of existence. the group of 20mg/kg Jiaweicitaowan(加未慈桃丸) extract treated group was showed 250% in ILS. 4. The effect of inhibition solid tumor was significantly decreased in both 10mg/kg, 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group S. The groups of 10mg/kg, 20mg/kg Jiaweicitaowan(加未慈桃丸) had significant effect of body weight change compared to control group. 6. Delayed type hypersensitivity was not significant in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 7. Hemagglutinin and Hemolysin titers were significantly increased by dose-dependent. so these results showed that the humoral immume respose was activated. 8. For the effect of rosette formimg cells was not significant in hoth Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 9. Natural killer cell activity was significantly increased in both Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group in the ratio of 100: 1, 50: 1 of effector and target cells, but in the ratio of 10:1, the Jiaweicitaowan(加未慈桃丸) extract treated groups were not significant. 10. The proliferation of lymphocyte and productivty of Interleukin-2 were significantly increased by dose-dependent in both 10mg/ kg, 20mg/ kg of Jiaweicitaowan(加未慈桃丸) extract treated groups as compared with control group. 11. In the phagocytic effect, the 20mg/kg of Jiaweicitaowan(加未慈桃丸) extract treated group showed the increasing effect with significance as compared with control group. According to the results, we can suggest that Jiaweicitaowan(加未慈桃丸) has the antitumor and the immunomodulatory effects.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• Journal of the Korean Chemical Society
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• v.34 no.4
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• pp.331-339
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• 1990

It has been studied that relations between electronic structure and anti-tumor activity by variation of amine group in cis-diamminedichloroplatinum (Ⅱ) complexes. We were also interested in these Pt (Ⅱ) complexes interaction with 1-methylcytosine of DNA base and the electronic structure of these complexes in order to understand the mechanism of the metal-nucleobases interaction. The results showed that net charge of center metal in Pt complexes effect anti-tumor activity. The mechanisgm of the bonding between metal and ligands largely based on charge transfer from ligand to metal atom. Furthermore, the established molecular orbitals showed that metal 6p-orbitals played an important role in the bonding scheme for the interactions between platinum (Ⅱ) complexes and 1-methylcytosine. We also found that the stronger Pt-N3 bonding strength became, the better anti-tumor agents were.

• Food Science and Biotechnology
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• v.18 no.1
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• pp.218-222
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• 2009

Ability of water extract from Prunella vulgaris Labiatae to stimulate immune system and inhibit tumor metastasis in mice was assessed. In experimental lung metastasis, prophylactic intravenous (i.v.) administration of water extract from P. vulgaris significantly inhibited lung metastasis in a dose-dependant manner. Peritoneal macrophages stimulated with P. vulgaris produced various cytokines such as tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-12 as well as induced tumoricidal activity. In an assay for natural killer (NK) cell activity, i.v. administration of P. vulgaris significantly augmented NK cytotoxicity. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum abolished the inhibitory effect of P. vulgaris on lung metastasis of colon26-M3.1 cells. These data demonstrate that P. vulgaris activate innate immune system to inhibit the growth of foreign materials including tumor cells in mice.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4039-4044
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• 2014

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.