• Nutrition Research and Practice
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• v.4 no.3
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• pp.177-182
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• 2010

The Chaga mushroom (Inonotus obliquus) has been used in folk medicine to treat cancers. However, limited information exists on the underlying anticancer effects of the major component of I. obliquus in vivo. We hypothesize that the pure compounds ($3{\beta}$-hydroxy-lanosta-8,24-dien-21-al, inotodiol and lanosterol, respectively) separated from I. obliquus would inhibit tumor growth in Balbc/c mice bearing Sarcoma-180 cells (S-180) in vivo and growth of human carcinoma cells in vitro. To test this hypothesis, the growth inhibition of each subfraction isolated from I. obliquus on human carcinoma cell lines (lung carcinoma A-549 cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and cervical adenocarcinoma HeLa cells) was tested in vitro. Then, after S-180 implantation, the mice were fed a normal chow supplemented with 0, 0.1 or 0.2 mg of subfraction 1, 2 or 3 per mouse per day. All of the subfractions isolated from I. obliquus showed significant cytotoxic activity against the selected cancer cell lines in vitro. Subfraction 1 was more active than subfraction 2 and subfraction 3 against the A549, AGS and MCF-7 cancer cell lines in vitro. In in vivo results, subfraction 1 isolated from I. obliquus at concentrations of 0.1 and 0.2 mg/mouse per day significantly decreased tumor volume by 23.96% and 33.71%, respectively, as compared with the control. Subfractions 2 and 3 also significantly inhibited tumor growth in mice bearing S-180 as compared with the control mouse tumor. Subfraction 1 isolated from I. obliquus showed greater inhibition of tumor growth than subfractions 2 and 3, which agrees well with the in vitro results. The results suggest that I. obliquus and its compounds in these subfractions isolated from I. obliquus could be used as natural anticancer ingredients in the food and/or pharmaceutical industry.

• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.1
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• pp.26-37
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• 2008

Objective : The present study was carried out to investigate the effects of NaisoOkseol-Tang (NOT) on solid tumor in mice in terms of immune-potentiating and direct cytotoxic action of NOT in vitro and vivo study. Methods: The present author investigated thymocyte proliferation and NO production to confirm immune-potentiating activity of NOT and also investigated body/tumor weight and survival rates in tumor bearing mice. In this study, administration of NOT decreased tumor/weight ratio significantly, and prolonged survival duration compared to non-treated control. Treatment with NOT also elevated proliferation rates of thymocytes isolated from tumor bearing mice. Results: In vitro study, treatment with NOT suppressed proliferation rate of Sarcoma 180 (S-180) cells. Contrary, treatment with NOT elevated proliferation rate of thymocytes. These results were co-related with in vivo study. In addition, NO production from abdominal macrophages isolated from normal mice was not affected by treatment with NOT. Conclusion : NOT is useful to treat patient with solid tumor, because NOT has direct toxic action for tumor cell and immune-potentiating action for T cells.

• Food Science and Biotechnology
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• v.15 no.1
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• pp.117-121
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• 2006

Ability of pectic polysaccharides isolated from Eleutherococcus senticosus EN-3 to inhibit tumor metastasis and induce antigen-specific immune response after oral administration in mice was assessed. Consecutive oral administration of EN-3 before tumor inoculation dramatically inhibited tumor metastasis produced by colon26-M3.1 and B16-BL6 cells. When Peyer's patch cells isolated from mouse intestine were co-cultured with EN-3, proliferation of Peyer's patch cells was induced. Mice co-administered with EN-3 and ovalbumin (OVA) showed significantly higher production of OVA-specific IgA in intestinal washing as well as IgG in serum than those administered with OVA alone. Payer's patch cells of mice immunized with OVA plus EN-3 showed much higher proliferating activity than those of mice immunized with OVA alone. Proliferating activity increased dose-dependently, indicating EN-3 specifically enhanced mucosal immune response to OVA. These results suggested EN-3 could significantly stimulate Peyer's patch cells either non-specifically or antigen-specifically, possibly playing important role in enhancement of mucosal and systemic immune systems.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7201-7205
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• 2014

Chemokine and chemokine receptor expression by tumor cells contributes to tumor growth and angiogenesis and thus these factors may be considered as tumor markers. Here we aimed to characterize cells directly extracted from glioma, meningioma, and secondary brain tumors as well as non-tumoral cells in vitro. Cells were isolated from brain tissues using 0.2% collagenase and characterized by flow cytometry. Expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, MCP-1 and IP-10 was defined using flow cytometry and qRT-PCR methods. Brain tissue isolated cells were observed as spindle-shaped cell populations. No significant differences were observed for expression of SDF-1, CXCR4, CXCR7, RANTES, CCR5, and IP-10 transcripts. However, the expression of CXCR4 was approximately 13-fold and 110-fold higher than its counterpart, CXCR7, in meningioma and glioma cells, respectively. CXCR7 was not detectable in secondary tumors but CXCR4 was expressed. In non tumoral cells, CXCR7 had 1.3-fold higher mRNA expression than CXCR4. Flow cytometry analyses of RANTES, MCP-1, IP-10, CCR5 and CXCR4 expression showed no significant difference between low and high grade gliomas. Differential expression of CXCR4 and CXCR7 in brain tumors derived cells compared to non-tumoral samples may have crucial impacts on therapeutic interventions targeting the SDF-1/CXCR4/CXCR7 axis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2439-2445
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• 2014

Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells.

• Nutritional Sciences
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• v.7 no.3
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• pp.144-150
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• 2004

We have investigated the effect of calcium spirulan(Ca-SP) isolated from a blue-green alga Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose and fructose, on invasion of both B16- BL6 melanoma cells, Colon 26 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters in a concentration-dependent manner. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no inhibitory effect on tumor cell migration to fibronectin-coated filters. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel- and laminin-substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin in a concentration-dependent fashion, while the pretreatment of laminin-substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contraset, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP in a dose-dependent manner. Seven intermittent ⅰ.ⅴ. injection of 100$\mu\textrm{g}$ of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung colonization of B16-BL6 melanoma cells in experimental metastasis model, by inhibiting the tumor invasion of basement membrane Matrigel, probably through the prevention of the adhesion and migration of tumor cells to laminin-substrate and of the heparanase activity.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.325.1-325.1
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• 2002

Cell motility plays important physiological roles in embryogenesis. immune defense. wound healing. and metastasis of tumor cells. Cell motility of normal cells is tightly regulated. while tumor cell motility is aberrantly regulated or autoregulated. Autotaxin (ATX) is a 125-kDa glycoprotein. originally isolated from the conditioned medium of human melanoma A2058 cells. ATX stimulates random (chemokinetic) and directed (chemotactic) motility of human tumor cells at high picomolar to low nanomolar concentrations. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5909-5913
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• 2012

Aims: We aimed to analyze the phenotype of tumor-infiltrating lymphocytes (TILs) and non-tumor infiltrating lymphocytes (NILs) in HCC and non-tumor tissues, and evaluate relationships between changes in these cells and the prognosis of HCC. Methods: Lymphocytes were isolated from HCC and corresponding non-tumor tissues and tested by flow cytometry. For comparison, clinical parameters were analyzed. Results: Compared with the non-tumor tissue, tumor tissue had a lower intensity of NK, NKT andCD8+T cell infiltration. TILs had higher intensity of CD4+CD25+Foxp3+regulatory T cell (Treg cells) infiltration compared with that in NILs. The prevalence of Treg cells was associated with fewer CD8 + T lymphocytes in the HCC immune microenvironment. The frequencies of NK cells and CD8+T cells in TILs of HCC patients with metastasis less than 12 months were lower than those without metastasis. However, the frequency of Treg cells was higher than those without metastasis. Conclusion: These results suggest that the frequencies of CD8+T, NK and NKT cells as well as Treg cells in the tumor tissue of HCC are significantly associated with patient survival, and could be applied as predictive indicators for HCC prognosis.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1211-1215
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• 2004

Ten coumarins were isolated from the root of Angelica dahurica by repeated silica gel column chromatography. Their chemical structures were elucidated on the basic of physicochemical and spectroscopic data. Among them, oxypeucedanin hydrate acetonide (7) was isolated for the first time from this plant. Cytotoxicity of coumarins isolated were determined in vitro against L1210, HL-60, K562, and B16F10 tumor cell lines by MTT method. Pangelin (5) and oxypeucedanin hydrate acetonide (7) showed a potent cytotoxic activity with the $IC_{50}$ values of 8.6 to 14.6 ${\mu}g$ /mL against four kinds of tumor cell lines. Other compounds showed the moderate cytotoxic activity or no activity against the tumor cell lines.