• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.41-52
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• 2009

Purpose: This study was designed to investigate the anti-tumor metastasis by immunomodulating effects of extracts of Prunellae Spica. Methods: Antimetastatic experiment was conducted in vivo by using colon 26-M3.1 carcinoma. And we observed cytotoxicity of Prunellae Spica on colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell, hela cell and macrophage. To observe the immnomodulating effects of Prunellae Spica, we estimated IL-6, IL-10, IL-12, TNF-${\alpha}$ from peritoneal macrophages. And we evaluated the activation of NK cell by using anti-asialo-GM1 serum. Results: We found that the administration of Prunellae Spica extracts significantly inhibited tumor metastasis in vivo. In an in vitro cytotoxicity analysis, cell growth are closer to 100% in case of colon 26-M3.1 carcinoma, L5178Y-R lymphoma cell, hela cell at low concentration. In case of macrophage, cell proliferation is closer to 100% less than $62.5{\mu}g/m{\ell}$ of Prunellae Spica extracts. The level of cytokine such as IL-6, IL-10, IL-12 which stimulates Prunellae Spica extracts was increased in dose-dependent manner compared to the control group. TNF-${\alpha}$ is hardly secreted less than $250{\mu}g/m{\ell}$ The depletion of NK cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Prunellae Spica on tumor metastasis. Conclusion: Prunellae Spica appears to have considerable activity on the anti-metastasis by activation the immune system such as macrophage and NK cell.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.1-14
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• 2003

Objective : Ikiyangeumhaedoc-tang(IYHT) has an effect of nourishing Yin(陰) and Jin(津), and has been used to cancer patient effectively. In order to prove the anticancer's and antimetastic effect of IYHT experimentally, studies were done. Methods : We evaluated the cytotoxic activity on HT-1080 cells as well as inhibitory effect on activity of DNA topoisomerase Ⅰ, cell adhesion, cell invasion and proliferation of HUVEC cells induced by bFGF and measured the expression of mRNA(uPA, MMP2, TIMP2), p-ERK protein, recovery effect of gap junctional intercellular communication by $H_{2}O_2$ and survival time of ICR mice bearing sacoma-180. Results : IYHT showed the inhibitory effect on DNA topoisomerase Ⅰ in the concentration of $100{\mu}g/ml,\;500{\mu}g/ml$ and the dosage-dependent inhibitory effect on the adhesion of HT-1080. The concentration of 1mg/ml of IYHT inhibited 15% of adhesion compared with control. IYHT decreased the expression of uPA, but not in MMP2, TIMP2 by RT-PCR and inhibited the expression of p-ERK effectively in the concentration of more than $500{\mu}g/ml.$ IYHT recovered the inhibited gap junctional intercellular communication by $H_{2}O_2$ to the level of 60% of normal control in the concentration of $400{\mu}g/ml$ but, did not extended the mean survival time of sarcoma 180-bearing mouse. Conclusions : It was concluded that IYHT could be applied usefully for prevention and treatment of human cancer, And also experimental study for the evaluation of molecular biological study and antimetastatic research would be recommended in the near future.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.4
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• pp.10-19
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• 2010

Methods: Intravenous administration of Platycodon grandiflorum was performed 2 days before tumor inoculation, then mice were killed 14 days after tumor inoculation, then number of tumor colonies were counted. Methanol extracts of Platycodon grandiflorum was added to colon26-M3.1 carcinoma cells, L5178Y-R lymphoma cells and Hela cells, and then cell growth was counted. To observe the immunomodulating effects of Platycodon grandiflorum, production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were measured with ELISA assay and the cell growth of macrophage were also counted. Furthermore, antimetastatic experiment after depletion NK cells by injection of anti-asialo GM1 serum was also administered. Results: Intravenous administration of Platycodon grandiflorum significantly inhibited metastasis of colon26-M3.1 carcinoma cells. In an in vitro cytotoxicity analysis, Platycodon grandiflorum affected tumor cell growth above specific concentration. As compared with control, the production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were incresed. And depletion NK cell completly abolished the inhibitory effect of metastasis. Conclusion: Platycodon grandiflorum appears to have considerable activity on immunomodulating effects and inhibit the metastasis of tumor. Further evaluation is needed for settling this.

• Natural Product Sciences
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• v.10 no.6
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• pp.284-288
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• 2004

We have recently reported that red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C. A. Meyer), showed immunomodulatory antitumor activities, mainly mediated by nitric oxide (NO) production by macrophage. In this study, we examined the effect of RGAP on anticancer activity using lung carcinoma 3LL, sarcoma 180 and adenocarcinoma JC tumor cells transplanted into mice as well as antimetastatic activity using B16-F10 melanoma. When RGAP (300 mg/kg) were treated to mice implanted with one of the three kinds of tumor cells, the tumor weight significantly decreased compared with control mice. Tumor inhibition ratios of RGAP (300 mg/kg) in mice transplanted with lung carcinoma 3LL, sarcoma 180 and adenocarcinoma JC cells were 26.8%, 29.3% and 31.6%, respectively. Hundred mg/kg of RGAP did not cause a significant decrease in tumor weight compared with control group. When RGAP was administered i.p. with the dose of 100 and 300 mg/kg in B16-F10 melanoma-bearing mice, lung metastasis were reduced significantly in mice. Corrected phagocytic index was also remarkably increased by RGAP. These results suggest that stimulation of phagocytic activity of macrophages may be a mechanism for in vivo anticancer and antimetastasis activities of RGAP.

• Journal of Haehwa Medicine
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• v.9 no.2
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• pp.97-109
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• 2001

To evaluate the antitumor activity and antimetastatic effects of HDBT, studies were done experimentally. The results were obtained as follows: 1. HDBT extracts didn't show cytotoxicity against BALB/C mouse lung fibroblast cell. 2. In cytotoxicity against A549, SK-OV-3, B16-BL6 and HT1080 concen- tration inhibiting cell growth up to below 30% of control was recognized at $10^{-3}g/ml$ of HDBT. 3. The concentration inhibiting adhesion of A549 and B16-BL6 to complex extracellular matrix up to below 30% of control was recognized at $10^{-3}g/ml$ of HDBT. 4. In Inhibitory effect on activity of DNA topoisomerase I, the $IC_{50}$ was shown $200-300{\mu}g/m{\ell}$ of HDBT. 5. The T/C% was 137.9% in HDBT-treated group in S-180 bearing ICR mice. 6. In CAM assay, HDBT extracts inhibited angiogenesis significantly at $15{\mu}g/egg$ concentration as compared with control. 7. In pumonary colonization assay, a number of colonies in the lungs were decreased but insignificantly in HDBT-treated group as compared with control group. 8. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC were decreased significantly in HDBT-treated group but numbers PLT were increased insignificantly as compared with control. From above results it was concluded that HDBT could be usefully applied for the prevention and treatment of cancer.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.488-495
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• 2019

Background: Timosaponin AIII (TA3) is a steroidal saponin extracted from Anemarrhena asphodeloides. Here, we investigated the anticancer effects of TA3 in MG63 human osteosarcoma cells. TA3 attenuates migration and invasion of MG63 cells via regulations of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, which are involved with cancer metastasis in various cancer cells. TA3 reduced enzymatic activities and transcriptional expressions of MMP-2 and MMP-9 in MG63 cells. TA3 also inhibited Src, focal adhesion kinase, extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), p38, ${\beta}-catenin$, and cAMP response element binding signaling, which regulate migration and invasion of cells. TA3 induced apoptosis of MG63 cells via regulations of caspase-3, caspase-7, and poly(ADP-ribose) polymerase (PARP). Then, we tested several ginsenosides to be used in combination with TA3 for the synergistic anticancer effects. We found that ginsenosides Rb1 and Rc have synergistic effects on TA3-induced apoptosis in MG63 cells. Methods: We investigated the anticancer effects of TA3 and synergistic effects of various ginseng saponins on TA3-induced apoptosis in MG63 cells. To test antimetastatic effects, we performed wound healing migration assay, Boyden chamber invasion assays, gelatin zymography assay, and Western blot analysis. Annexin V/PI staining apoptosis assay was performed to determine the apoptotic effect of TA3 and ginsenosides. Results: TA3 attenuated migration and invasion of MG63 cells and induced apoptosis of MG63 cells. Ginsenosides Rb1 and Rc showed the synergistic effects on TA3-induced apoptosis in MG63 cells. Conclusions: The results strongly suggest that the combination of TA3 and the two ginsenosides Rb1 and Rc may be a strong candidate for the effective antiosteosarcoma agent.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.317-329
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• 2002

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.726-733
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• 2005

Histone deacetylase (HDAC) inhibitors target key steps of tumor development. They inhibit proliferation, induce differentiation and/or apoptotic cell death, and exhibit potent antimetastatic and antiangiogenic properties in cancer cells in vitro and in vivo. Although they are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. The present study was undertaken to investiate the underlying mechanism of a HDAC inhibitor trichostatin A (TSA)-induced growth arrest and its effect on the cell cycle control gene products in a human lung carcinoma cell line A549. TSA treaoent induced the growth inhibition and morphological changes in a concentration-dependent manner. Treatment of A549 cells with TSA resulted in a concentration-dependent increased G1 (under 100 ng/ml) and/or G2/M (200 ng/ml) cell population of the cell cycle as determined by flow cytometry Moreover, 200 ng/ml TSA treatment significantly induced the population of sub-G1 cells (23.0 fold of control). This anti-proliferative effect of TSA was accompanied by a marked inhibition of cyclins, positive regulators of cell cycle progression, and cyclin-dependent kinases (Cdks) expression and concomitant induction of tumor suppressor p53 and Cdk inhibitors such as p21 and p27 Although further studies are needed, these findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of TSA in human lung carcinoma cells.

• Archives of Pharmacal Research
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• v.29 no.3
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• pp.224-234
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• 2006

We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.213-219
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• 2011

The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.