• 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.

• Korean Journal of Pharmacognosy
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• v.41 no.2
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• pp.115-121
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• 2010

The present study was designed to explore an immunostimulating activity of crude extracts of Macrolepiota procera, and a combination therapy of cisplatin and Macrolepiota procera extracts which can potentiate the anti-cancer activity of cisplatin. For these, water extraction of Macrolepiota procera were performed at $4^{\circ}C$(MPE-4) and $100^{\circ}C$(MPE-100). In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of MPE ($80-2,000{\mu}g$/mouse) inhibited tumor metastasis compared with tumor control. Peritoneal macrophages stimulated with MPE produced IL-12 as well as induced tumoricidal activity. In an analysis of NK-cell activity, i.v. administration of MPE ($200{\mu}g$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin ($20{\mu}g$) and MPE ($100{\mu}g$) exhibited prolongation of lifespan in colon26-M3.1 tumor bearing mouse. These results suggested that MPE stimulate immune system non-specifically and application as adjuvant in cancer treatment.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.861-867
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• 2003

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 $\mu$ g/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity. i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

• Radiation Oncology Journal
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• v.38 no.1
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• pp.1-10
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• 2020

Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.

• Korean Journal of Plant Resources
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• v.24 no.3
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• pp.298-303
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• 2011

A large number of edible seaweeds are consumed by the coastal peoples of Asia. Some of them are used in traditional remedies in many parts of the world. In this study we investigated effects of supplementation with ethyl acetate extracts of the brown alga Eisenia bicyclis (EBE) on rat macrophage to evaluate the possibilities as immune-modulators. Twelve male SD rats were divided into two groups and the treatments were as follows: A, no Eisenia bicyclis extract (EBE) intake and distilled water ; B, oral supplemented with EBE 200 mg/kg. After 5 weeks of supplementation, rats were sacrificed to assess the effect on peritoneal macrophage functions. We showed no increasing effects on tumoricidal activity, phagocytic activity and NO production in macrophages in EBE supplementation group. However, EBE supplementation suppressed NO-iNOS production and p65 translocation into the nucleus in LPS-stimulated macrophages. Overall, these results suggest that the supplementation of EBE might have an anti-inflammatory effects on NO-iNOS production in macrophages throughout the inhibition of NF-${\kappa}B$ activation.

• Journal of Ginseng Research
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• v.33 no.3
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• pp.177-182
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• 2009

Macrophages play an important role in the first line of immunologic effects against tumor cells. The effects of nonsaponin red ginseng (NSRG) components on macrophage functions like tumoricidal activity, phagocytic activity, and NO production in young (8-weeks-old) and aged (82-weeks-old) male C57BL/6 mice were assessed in vitro, respectively. The treatment of tumor cells (melanoma B16 cells) with the supernatants of NSRG-treated macrophages resulted in an increase of cytotoxicity at 300 $\mu$g/ml in the aged mice, whereas the supernatants did not have a cytotoxic effect in the young mice. It was observed that the supernatants induced the increase of tumor cell proliferation at 150 $\mu$g/ml in the young mice, suggesting that the supernatants contain growth factors rather than cytotoxic molecules. In addition, NSRG alone had a direct cytotoxic effect on the B16 tumor cells. NSRG had no effect on the NO production by the macrophages in the young mice, while it significantly increased the level of NO release in the aged mice. There was no difference in the phagocytic activities of the macrophages by NSRG in both groups of mice. These results suggest that NSRG has differential effects on the macrophage functions in young and aged mice.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.941-950
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• 2012

In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1771-1779
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• 2015

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Presently, targeted therapy via monoclonal antibodies to specific tumor-associated antigens is being continuously developed. Hep88 mAb has proven to exert tumoricidal effects on the HepG2 cell via a paraptosis-like morphology. To verify the pathway, we then demonstrated downstream up-regulation of caspase-3, caspase-8 and caspase-9, assessingmRNA expression by real-time PCR and associated enzyme activity by colorimetric assay. Active caspase-3 determination was also accomplished by flow cytometry. Active caspase-3 expression was increased by Hep88 mAb treatment in a dose-and time-dependent manner. All of the results indicated that Hep88 mAb induced programmed cell death in the HepG2 cell line from paraptosis-like to apoptosis by downstream induction of caspases. These conclusions imply that Hep88mAb might be a promising tool for the effective treatment of HCC in the future.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.78-78
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• 2003

Inulin, an active component of Chicorium intybus root, has been shown to stimulate the growth of bifidobacteria, and inhibit colon carcinogenesis. NO mediates a number of the host-defense functions of activated macrophages, including antimicrobial and tumoricidal activity. We examined the effect of inulin on the synthesis of NO in RAW 264.7 cells. Inulin alone had no effect, whereas inulin with IFN-ν synergistically increased the NO production and inducible NO synthase (iNOS) expression in RAW 264.7 cells. Synergy between IFN-ν and inulin was mainly dependent on inulin-induced TNF-${\alpha}$ secretion. Also, protein kinase C (PKC)-${\alpha}$ was involved in the inulin-induced NO production. Inulin-mediated NO production was inhibited by the protein tyrosine kinase (PTK) inhibitor, tyrphostin AG126. Since iNOS gene transcriptions have been shown to be under the control of the NF -$\kappa$B/Rel family of transcription factors, we assessed the effect of inulin on NF -$\kappa$B/Rel using an EMSA. Inulin produced strong induction of NF-$\kappa$B/Rel binding, whereas AP-l binding was slightly induced in RAW 264.7 cells. Inulin stimulated phosphorylation and degradation of I$\kappa$B-${\alpha}$. These results suggest that in IFN-ν-primed RAW 264.7 cells inulin might stimulate NO synthesis via activation of PKC-${\alpha}$ and PTK, resulting in the activation of NF-$\kappa$B.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.11
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• pp.1639-1645
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• 2002

The purpose of this study was to investigate the effects of aflatoxin $B_1$ ($AFB_1$) on the ultracellular morphology alteration, apoptosis induction and reactive nitrogen and oxygen intermediates production of peritoneal macrophages (DPM) from mule ducks. The ducklings were purchased from a commercial hatchery, and were fed a corn-soybean based diet. As the ducklings were grown up to 3 wk of age, the Sephadex-elicited peritoneal exudative cells (PEC) were used as the source for duck peritoneal macrophages. The ultracellular morphology study showed that significant number of cells shifted from category I (normal cell with ruffled membrane) and II (cell membrane blebbing) to category III (cell membrane blebbing and even rupture) after DPM were incubated with $AFB_1$ ($20{\mu}g/ml$) for 12 to 48 h. When DPM were exposed to $AFB_1$ in vitro, the production of NO, $H_2O_2$ and $O_2{^-}$ in macrophages was reduced after 12-48 h incubation with previous LPS stimulation. There was a DNA laddering pattern observed in DPM incubated with $AFB_1$ 5, 10, 20, 50 or $100{\mu}g/ml$ for 12 h. Evidence also revealed that the percentage of apoptotic cells was increased along with the elevation of $AFB_1$ concentration. The results suggest that $AFB_1$ exposure causes duck macrophages going on apoptotic pathway through evidence of ultracellular morphology alteration and DNA laddering in agarose electrophoresis. The production of reactive nitrogen and oxygen intermediates of duck macrophages also depressed after $AFB_1$ exposure, and this implied that $AFB_1$ could cause deteriorated functions of bacteriocidal and tumoricidal activity in duck macrophages.