• Title/Summary/Keyword: anti-metastasis

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Anti-metastasis Activity of Black Rice Anthocyanins Against Breast Cancer: Analyses Using an ErbB2 Positive Breast Cancer Cell Line and Tumoral Xenograft Model

  • Luo, Li-Ping;Han, Bin;Yu, Xiao-Ping;Chen, Xiang-Yan;Zhou, Jie;Chen, Wei;Zhu, Yan-Feng;Peng, Xiao-Li;Zou, Qiang;Li, Sui-Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6219-6225
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    • 2014
  • Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

Anti-metastatic mechanism of mountain cultivated wild ginseng in human cancer cell line

  • Jang, S.B.;Lim, C.S.;Jang, J.H.;Kwon, K.R.
    • Journal of Pharmacopuncture
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    • v.13 no.1
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    • pp.37-43
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    • 2010
  • Objective : Ginseng is one of most widely used herbal medicine. Ginseng showed anti-metastasis activities. However, its molecular mechanisms of action are unknown. So we want to report the wild ginseng repress which plays key roles in neoplastic epithelial-mesenchymal transition process. Methods : Treatment of the human colorectal carcinoma LOVO cells and human gastric carcinoma SNU601 cells with the increased concentrations of cultivated wild ginseng extracts resulted in a gradual decrease in the AXIN2 gene expression. Results : Metastasis-suppressor genes, maspin and nm23 was not affected by the treatment of ginseng extracts in LOVO cells. Moreover, the mountain cultivated wild ginseng or mountain wild ginseng are similar in their inhibitory effects on the expression of AXIN2 gene, but are substantially stronger than cultivated ginseng. Conclusion : We described the novel mechanism of wild ginseng-induced anti-metastasis activity by repressing the expression of AXIN2 gene that plays key roles in epithelial-mesenchymal transition process.

Inhibitory Effect of Ligularia Stenocephala on the Cancer Metastasis

  • Lee, Dong-Keon;Kim, Jin-Kyu;Kim, Jong-Soo;Park, Kyoung-Jae;Cha, Dong-Seok;Jeon, Hoon
    • Natural Product Sciences
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    • v.18 no.2
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    • pp.89-96
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    • 2012
  • Ligularia stenocephala has been used as a traditional medicine for the treatment of asthma, arthritis, jaundice, and hyperpiesia. In this study, we investigated the anti-metastatic and hypnotic effects of the methanolic extract of L. stenocephala (MLS). Gelatin zymographic analysis revealed that MLS suppresses matrix metalloproteinase-2 (MMP-2) and MMP-9 activities in B16F10 cells. The gene expressions of MMPs were also down-regulated by MLS treatment in a dose-dependent manner. In addition, cancer cell invasion and migration were attenuated by MLS via suppression of NF-${\kappa}B$ activation. The in vivo lung metastasis of B16F10 melanoma cells was also inhibited by the treatment of MLS. These findings show that MLS has anti-metastatic properties, and, therefore, it might be applicable as a valuable anti-metastatic agent.

The Study on Anti-Metastasis and Immune Activation of Carthami Semen Herbal Acupuncture (홍화자약침(紅花子藥鍼)의 암전이 억제와 면역 활성화에 관한 연구)

  • Park, Ki-Chul;Park, Hee-Soo
    • Journal of Acupuncture Research
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    • v.23 no.6
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    • pp.45-60
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    • 2006
  • Objectives : This study was guided to estimate inhibitory effects against hepatic metastasis and activation of immunocytes by Carthami Semen Herbal Acupuncture. Methods : Colon26-L5 carcinoma cells were injected through hepatic portal vein to induce hepatic metastatic cancer. Changes in weight, morphology of the cancer were estimated and cytokine level was analyzed to produce immunological changes. Results: The experimental group was significantly decreased metastatic size and proliferation compared with the control group. Observing immunocytes from the spleen of experimental group T-lymphocytes were significantly increased. As compared with control group, the differentiation of total T cell, helper T cell, cytotoxic T cell, Macrophage and NK cell was increased. Measuring the level of cytokine $IFN-{\gamma}$ which stimulates Th 1 was significantly increased in splenocyte with Con A stimuli. $IFN-{\gamma}$ and IL-12 were significantly increased in peritoneal exudate macrophage with LPS stimuli. Conclusion : These findings strongly indicate Carthami Semen Herbal Acupuncture improves immunity to inhibit the growth of cancer and metastasis.

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The Effects of HangAmDan(HAD) on Anti-Metastasis and Preventing Relapses, Administered to 69 Cancer Patients (각종 암환자 69례에 대한 항암단의 항전이 및 재발억제효과)

  • Lee, Yong-Yeon;Song, Kee-Cheol;Choi, Byung-Lyul;Seo, Sang-Hoon;Cho, Jung-Hyo;Lee, Yeon-Weol;Son, Chang-Gue;Cho, Chong-Kwan;Yoo, Hwa-Seung
    • The Journal of Internal Korean Medicine
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    • v.23 no.2
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    • pp.165-173
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    • 2002
  • Purpose : Among numerous biological symptoms of cancer, matrix metalloproteinases (MMPs) are essential for tumor invasion and metastasis. HAD is used as an inhibitor of MMP gene. This study was designed to evaluate the effects of HAD on anti metastasis and preventing recurrence in cancer patients. Materials and Methods : We retrospectively analyzed the medical records of 69 cancer patients who had been administered with HAD for over 12 months continuously in East-West Cancer Center of Oriental Hospital of Daejeon University, from January 1993 to May 2002. Results : We analyzed gender, portion, stage and anti-metastasis & recurrence rates of cancer patients. Analysis of sex cases showed that the percentage of male is 62.3%, female is 37.7%. Analysis of cancer portion showed that the percentage of stomach is 31.9%, colorectum is 26.1%, lung is 21.7%, liver is 8.7%, breast is 8.7% Analysis of stage showed that the rate of III is 78.3%, IV is 13.0% and II is 8.7%. Analysis of anti-metastasis and recurrence rates showed that colorectal cancer is 77.8%, stomach cancer is 63.6%, lung cancer is 33.4% and breast cancer is 33.3% (mean : 53.6%). Conclusions : HAD has significant effects on anti-metastasis and preventing recurrence of tumor on cancer patients. So it helps to prolong the survival rates of cancer patients.

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D. candidum has in vitro anticancer effects in HCT-116 cancer cells and exerts in vivo anti-metastatic effects in mice

  • Zhao, Xin;Sun, Peng;Qian, Yu;Suo, Huayi
    • Nutrition Research and Practice
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    • v.8 no.5
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    • pp.487-493
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    • 2014
  • BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.

Interleukin-9 Inhibits Lung Metastasis of Melanoma through Stimulating Anti-Tumor M1 Macrophages

  • Park, Sang Min;Do-Thi, Van Anh;Lee, Jie-Oh;Lee, Hayyoung;Kim, Young Sang
    • Molecules and Cells
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    • v.43 no.5
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    • pp.479-490
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    • 2020
  • Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4+ T cells, CD8+ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.

Effects of Orostachys Japhonicus Herbal-Acupuncture on Transferred Hepatic Cancer of Mouse Induced by Colon26-L5 Human Colon Cancer Cells (와송(瓦松) 약침(藥鍼)이 mouse의 간전이 암모델에 미치는 영향)

  • Sohn, Seong-Hyoun;Park, Hee-Soo
    • Journal of Acupuncture Research
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    • v.23 no.6
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    • pp.61-76
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    • 2006
  • To study the effects of anti-cancer, anti-metastasis and immune response improvement effects of herbal-accupunture with Orostachys japhonicus A.Berger, infusion solution put into Kansu(BL18) of mouse induced by Colon26-L5 human colon cancer cells, which are corresponding to humanbody. We observed the change of body weight, surviving number, median surviving time, increase of life span, changes in amount of leukocyte, erythrocyte, platelet, total protein, creatinine, glucose and LDH, weight of spleen and kidney, histological analysis on tissue metastasis of liver, splenic cell proliferation, the expression of cytokine gene, the number of CD4+, CD8+, CD9+ and NK cell, and concluded like this. The results were obtained as follows ; 1. In acute and sub-acute cytotoxicity experiment, significantly signs were not appeared in all groups. 2. Antimetastatic experiment in vitro and in vivo showed that Orostachys Japhonicus A.Berger Herbal-acupuncture at Kansu(BL18) has antimetastatic effects. 3. The spleen cells proliferation of the experimental groups treated with Orostachys Japhonicus A.Berger infusion solution extract has increased significantly compared with that of the control group. 4. As compared with control, the population of total T cell, helper T cell, cytotoxic T cell and macrophage were increased. 5. The production of Th 1 type cytokines from splenocyte and cytokines which is associated with anti-tumor activity form macrophage were increased significantly. Above the results revealed that herbal-accupunture with Orostachys Japhonicus A.Berger infusion solution has effects of anti-cancer, anti-metastasis and immune response improvement.

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Screening of mushroom having anti-angiogenic activity for development of new cancer metastasis Inhibitor (버섯으로부터 새로운 암전이 억제물질 개발을 위한 혈관신생 억제물질의 탐색)

  • Jeong, Seung-Chan;Kim, Jae-Ho;Park, Jeong-Sik;Lee, Jong-Soo
    • Journal of Mushroom
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    • v.1 no.1
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    • pp.44-47
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    • 2003
  • This study was carried out to obtain new cancer metastasis inhibitor from mushrooms. Extracts from 52 isolates belong to 7 species of mushrooms were prepared by water, ethanol and methanol extractions and its anti-angiogenic activity were investigated by choriollantoic membrane(CAM) assay. Water extracts of Fomitella fraxinea ASI 17003 and ASI 17009 fruiting bodies, ethanol extract of Pholiota sp. ASI 24008 and Grifola frondosa ASI 9017 fruiting bodies and methanol extract of Inonotus obliquus ASI 74012 mycelia had the potential anti-angiogenic activity of 62.5%~68.8%. Finally, Pholiota sp. ASI 24008 was selected as a producer of cancer metastasis inhibitor on the basis of their solid yield and anti-angiogenic activity, etc.

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Anti-Metastatic Activity of Glycoprotein Fractionated from Acanthopanax senticosus, Involvement of NK-cell and Macrophage Activation

  • Ha, Eun-Suk;Hwang, Soo-Hyun;Shin, Kwang-Soon;Yu, Kwang-Won;Lee, Keyong-Ho;Choi, Joo-Sun;Park, Woo-Mun;Yoon, Taek-Joon
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.217-224
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    • 2004
  • Previously, we reported that water-extracted Acanthopanax senticasus exhibited anti-meta-static activity by stimulating the immune system. In this study, we fractionated glycoproteins (EN-SP) from the soluble protein layer (GF-AS) of A. senticasus and determined their basic chemical properties. We also investigated the anti-tumor and immunostimulating activities of the fractionated glycoprotein, EN-SP. We found that intravenous (i.v.) administration of GF-AS dramatically inhibited metastasis of colon26-M3.1 carcinoma cells to the lung in a dose-dependent manner. In vitro analysis showed GF-AS to enhance the proliferation of splenocytes. GF-AS also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-1$\beta$, TNF-$\alpha$, IL-12 and IFN-${\gamma}$. Furthermore, the production of these cytokines was partially blocked when peritoneal macrophage was cultured with the polyclonal antibodies against GF-AS. The depletion of NK cells by rabbit anti-asialo GM1 serum partly abolished the inhibitory effect of GF-AS on lung metastasis of colon26-M3.1 cells. Using gel filtration, EN-SP, an active glycoprotein fraction, is isolated from GF-AS. While both GF-AS and EN-SP stimulated the proliferatation of splenocytes of normal mice, EN-SP showed higher anti-metastatic activity and more potently stimulated the proliferation of splenocytes compared to GF-AS. These results suggest the use of EN-SP, the fractionated glycoprotein from A. senticasus, can be used as a therapeutical reagent to prevent or inhibit tumor metastasis.