• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.2
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• pp.20-52
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• 1999

In order to investigate the effect of Naetakchungumsankamibang(NTCGS) water extract on the skin tumor induced by 3-MCA and immunological responses in mice, the cytotoxicity against SK-MEL-2 cells and total number of tumors induced by 3-MCA were measured. The numbers of WBC, platelets and RBC, plaque forming cells, hemagglutinin titer, hemolysis titer, carbon clearance, proliferation of splenocyte by thymidine uptake assay, splenic leukocyte by FACS analysis and $TNF-{\alpha}$ were also measured for the evaluation of the immunological responses. The results were obtained as follows: 1. In cytotoxicity against SK-MEL-2 cells, concentration inhibiting cell growth up to below $20\%$ of control was recognized at 1mg/ml of NTCGS. 2. In Inhibitory effect on the skin tumor induced by 3-MCA, the results showed a strong inhibitory effect of NTCGS. 3. In hematological changes in the tumor bearing mice, the numbers of WBC decreased significantly in NTCGS treated group as compared with control. 4. In hematological changes in the tumor bearing mice, the numbers of platelets increased significantly in NTCGS treated group as compared with control. 5. In hematological changes in the tumor bearing mice, the numbers of RBC increased with no significance in NTCGS treated group as compared with control. 6. Effects of the plaque forming cells in the tumor bearing mice, NTCGS treated group exhibited a significant effect compared with control. 7. In terms of the effects on hemagglutinin titer, NTCGS treated group showed higher level than control, without significance. 8. In terms of the effects on hemolysis titer, NTCGS treated group showed higher level than control, without significance. 9. In terms of the effects on phagocytic index K in Balb/C mice, NTCGS treated group showed significant difference from control. 10. In terms of the effects on proliferation of splenocyte by thymidine uptake assay, NTCGS showed significant effect at the concentration of 0.5mg/ml. 11. In terms of the effects on splenic leukocyte of Balb/C mice by FACS analysis, NTCGS treated group showed significantly higher level of helper T cell, B cell and macrophage than in control. 12. In terms of the effects on the secretion of $TNF-{\alpha}$, the treated group showed significant effect at the concentration of 1mg/ml of NTCGS. Based on the results summarized above, NTCGS is considered to have antitumor activity and immunological responses against skin tumor, and to be usable fur the treatment.

• Journal of Pharmacopuncture
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• v.10 no.1 s.22
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• pp.85-100
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• 2007

Objectives : This research was executed to verify antitumor effect and protective effect on doxorubicin(Doxo)-induced toxicity of Cultivated Wild Ginseng(CWG) and synergic effect of CWG with Doxo in B16/F10 melanomas-bearing C57BL/6 mice. Methods : To evaluate protective effect on doxorubicin(Doxo)-induced toxicity and enhancing effect on the antitumor activity of Doxo, CWG water extract(0.5 ml) was intraperitoneally injected for 10 days, in combination with intraperitoneal injection of Doxo(4 mg/kg) on days 12, 16, 19, to mice subcutaneously inoculated with $2{\times}10^6/ml$ B16/F10 melanoma cells. In order to investigate antitumor effect of CWG, CWG water extract(0.5 ml) was intraperitoneally injected for 10 days to mice subcutaneously inoculated with $2{\times}10^6/ml$ B16/F10 melanoma cells. Results : The body weights of melanoma-bearing mice increased following B16/F10 cells inoculation. In contrast, such an increase in body weights was significantly attenuated by Doxo administration. Whereas CWG inhibits the decrease in body weights induced by Doxo. The tumor volume and tumor weights of melanomas-bearing mice dramatically increased following B16/F10 cells inoculation, In contrast, such an increase in tumor volume and tumor weights were significantly attenuated by Doxo or CWG administration. But the synergic effect of CWG with Doxo was not observed. The reduction of cellularity of seminiferous epithelia, level of spermatogonium and spermatid induced by Doxo was recovered by CWG administration. BrdU labeling index of spermatogonium was remarkably decreased in Doxo group but was no change in CWG group. Whereas the incidence and intensity of BrdU labelled spermatocytes and spermatids were increased by CWG administration than those of Doxo group. Conclusions : The obtained results suggest that CWG have antitumor effect and protective effect on doxo-induced testicular toxicity. This effect might be mediated through the supplementation of vital energy.

• Toxicological Research
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• v.17 no.2
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• pp.151-157
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• 2001

Neutropenia is a major dose-limiting side effect of cancer chemotherapy. The therapeutic effect of HM 10411 was examined on neutropenia caused by anticancer agents. Neutropenia in normal ICR mice was induced by a single combined intraperitoneal injection of 130 mg/kg of cyclophosphamide (CPA). 4.5 mg/kg of doxorubicin (DXR). and 1 mg/kg of vincristine (VCR) on day O. Neutropenia in tumor-bearing mice was made by a single intraperitoneal injection of 200 mg/kg of cyclophosphamide (CPA) into BALB/c mice bearing Colon 26 adenocarcinoma at 7 day after tumor implantation. HM 10411 or filgrastim (100 $\mu\textrm{g}$/kg/day) was subcutaneously administered for 5 consecutive days starting 1 day after injection of anticancer agents in order to stimulate neutrophil production. Injection of HM 10411 accelerated the recovery from these anticancer drug-induced neutropenia. In normal and tumor-bearing mice. neutrophil production efficacy of HM 10411 was similar than that of filgrastim. These results suggest that HM 10411 could be useful in the clinical treatment for neutropenia induced by anticancer agents.

• Archives of Pharmacal Research
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• v.20 no.2
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• pp.128-137
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• 1997

The effects of cylindan, a polysaccharide isolated from the basidiocarps of Agrocybe cylindracea, on murine sarcoma 180 tumor and murine immune cells were examined after intraperitoneal administration. Cylindan exhibited a marked life extension effect in mice against ascite forms of sarcoma 180 and Lewis lung carcinoma at a dose of 50 mg/kg/day, although it did not show any direct cytotoxicity against sarcoma 180, X5563, and MM46 murine tumor cells. Cylindan increased numbers of bone marrow stem cells as well as peritoneal exudate cells in flow cytometry using monoclonal antibodies. The tumor bearing mice group apparently showed the increase of macrophages and cytotoxic T lymphocytes in mouse spleen cells during the early stage of tumor growth. But during the later stage, the control group decreased immune cells and cylindan restored the decreased immune cells in the tumor bearing mice to the normal level. In non-specific immune response, cylindan stimulated the bacterial phagocytosis and acid phosphatase production in macrophages. It also activated components of the alternative complement pathway and natural killer activity against YAC-1 lymphoma. In number of plasma cells as token of stimulation of the differentiation of B lymphocytes. In cellular immunity, cylindan restored the depressed response of delayed type hypersensitivity in the tumor bearing mice to 60% of the normal level and increased the interleukin-2 (IL-2) responsiveness in the IL-2 dependent CTLL-2 cells. These results suggest that cylindan did not show direct cytotoxic effects on tumor cells but restored the decreased immune response of the tumor bearing mice.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.121-128
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• 1995

Purpose: The enhanced cytotoxic effect of combined treatment of hyper-thermia and chemotherapy by increasing intracellular acidity with HMA was investigated. Materials and Methods: FSall tumor cells were injected on the hindlegs of female $C_3H$ mice. When the tumor volume reached about 200mm3, experiments were performed on the groups classified as follows: Group I :Control, Group II : Melphalan alone (2.5mg/kg, 5mg/kg, 10mg/kg, 15mg/kg), Group III : Heat alone $(42.5^{\cdot}C$ for 1 hour) Group IV : Melphalan + Heat $(42.5^{\cdot}C$ for 1 hour), Group V : HMA(10mg/kg) + Melphalan(5.0mg/kg) + Heat$(42.5^{\cdot}C$ for 1hour). Each group included 8-12 mice on each experiment HMA (3-amino-6-chloro-5-(1-homopiperidyl )-N-(diaminomethylene) -c-pyrazinecarboxamide), an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoxide (DMS) and injected into the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of melphalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor volme reached at $1500mm^3$ Excision assay was performed on each group and repeated 2-4 times. Results : Tumor growth delay of each experimental groups at $1500mm^3$ were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using FSall tumor cells, the cytotoxicity of each experimental groups was $1.2{\times}10^7,\;1{\times}10^7,\;6{\times}10^6,\;1.7{\times}10^6\;and\;1{\times}10^5$ clonogenic cells/gm respectively When HMA was added to the combined treatment of heat and .chemotherapy, the tumor growth was delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at $1500mm^3$ of tumor volume. Conclusion: The combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.211-232
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• 1998

Because there were lots of side effects and tolerances to the existing anticancer therapeutics, the experiment extracting the anticancer effect from medicinal herbs is in progress liviely. Therefore the purpose of this study were to research the tendency and the course of anticancer studies. To research the tendency of anticancer studies, medicinal herbs of fifty three experimental papers were analyzed and to examine the course of studies, anticancer papers in the medical world were used. The obtained results were as follows: Methods of herbal medicinal treatments were elimination the pathogenic factor(祛邪) and supporting healthy energy(扶正) method used. In this study, immediately tumor bearing and immune response were the most important point. The subject of immediately tumor bearing was not in the specific cancer but in the influence on the life span of general cencerous cells. In the experimental study of immune response, the effect on NK cell activity of medicinal herbs most studied. The combined usage of medicinal herbs and anticancer agent mostly intended to know whether it inhibits the tumor cell growth. The serum test and blood cell number test show if medicinal herbs inhibit side effect of anticancer agent. More than 80 percents of used medicinal herbs, there were anticancer activities. However anticancer experimental studies using medicinal herbs two weak points. The one, it was difficult to choose a prescription according to differentiation of symptoms and signs(辨證論) of the Oriental Medicine, because we put to the test not a man but a mouse. The other, as we observed the indirect effect of the whole physiological regulation caused by synergic effects of the complex prescription, we don't understand the detailed mechanism of the herb. Therefore, if the anticancer effect of the herb is proved the experiment, we should research the concrete medical action of medicinal herbs and immunological analysis of herbal medicines to the body.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.47-54
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• 2014

The aim of this study is to evaluate the effects of green tea polyphenol (GTP) on anticancer treatment with cisplatin (CP), using both an in vitro cell culture model and an in vivo mouse model of established breast tumor. Mouse breast cancer cells (EMT6) were treated with or without GTP and CP followed by determination of the cell viability using an MTT assay. The relative cell viability of CP treated EMT6 cells was 96% at a 20 ${\mu}g/mL$ concentration of cisplatin; however, in combination with GTP (50 ${\mu}g/mL$), the cell viability decreased to 20% at the same concentration of CP (20 ${\mu}g/mL$). For the in vivo study, EMT6 cells were inoculated into Balb/c mice for the establishment of a tumor-bearing mice model. The tumor-bearing mice were treated with CP (5 mg/kg. i.p.) with or without dietary GTP (0.2% drinking water). Tumor growth was monitored by a measurement of tumor size using a digital caliper, and nephrotoxicity was determined by enzymatic and histological examinations. The levels of p53 and caspase-3 in tumor tissues were examined by a Western blot. In tumor-bearing mice treated with GTP plus CP, the increment of tumor volume showed a significant reduction, compared with CP or GTP alone. The levels of p53 and cleaved caspase-3 (caspase-3/p17) in tumor tissues of tumor-bearing mice were increased by CP and GTP compared to CP alone. In CP treated tumor-bearing mice, ${\gamma}$-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) activities were decreased, and marked tubular necrosis and dilatation were observed in the kidney. CP-induced enzymatic and histopathological changes in the kidney of tumor-bearing mice were reduced by combinations of GTP with CP. The results of these experiments demonstrated that dietary GTP has a potentiating effect on CP anti-tumor activity and a protective effect against CP-induced renal dysfunction. Therefore, GTP may be used as a modulator in anticancer treatment with CP.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.242-251
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• 2004

In this piece of research, Prunellae spica is added to Sambonggangyongbaneotang for one group and Trionycis carapax is added to Sambonggangyongbaneotang for the other group. With these two different prescriptions, the degrees of tumor suppression are compared to develop a better prescription. SKH = Sambonggangyongbaneo-tang + Prunellae Spica SKB = Sambonggangyongbaneo-tang + Trionycis Carapax The results were as follows: 1. SKH and SKB demonstrated anti-tumor effects against tumor advancement of S-180 2. SKH and SKB showed on elevation of macrophage for tumor-bearing mice. 3. $100{\mu}g/ml,\;500{\mu}g/ml$ of SKH and $500{\mu}g/ml$ of SKB demonstrated a rise in alkaline phosphates of B-Lymphocyte in the spleen in tumor-bearing mice. Results support a role for both SKH and SKB for anti-tumor effects via endorsement of macrophage and encouragement of B-lymphocyte toward S-180.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1036-1046
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• 2015

Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.