• Natural Product Sciences
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• 제28권2호
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• pp.80-88
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• 2022

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

• Archives of Pharmacal Research
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• 제20권6호
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• pp.539-544
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• 1997

Anti-metastatic activities of IH901, an intestinal bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo. Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT 1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

• 동의생리병리학회지
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• 제17권2호
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• pp.525-528
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• 2003

Spatholobus Suberectus dunn. has been applied to blood stasis in oriental medicine. We selected one potent ethyl acetate subfraction-2 from Spatholobus Suberectus Dunn.(SSD) from anti-metastasis screening. It exerted the cytotoxicity against HT1080 and B16BL6 with the IC50 of 60 ug/ml and also significantly inhibited tumor cell induced platelet aggregation (TCIPA). It effectively didn't inhibit cell adhesion of HT1080 to matrigel coated wells, while it inhibited the cell invasion of HT1080 at the doses of 10, 20, 40 μg/ml by Boyden chamber assay. It effectively suppressed lung metastasis by B16BL6 melanoma in C57BL6 mice. These results indicate that the EtOAc subfraction-2 of Spatholobus Suberectus Dunn. can be applied to caner treatment with anti-metastatic activity.

• 생약학회지
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• 제36권4호통권143호
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• pp.332-337
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• 2005

We here demonstrate the evidence of increased anti-tumor and immunostimulating activities of crude extracts (GAL) from Galium. aparine L. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma cells, prophylactically intravenous (i.v) administration of GAL significantly inhibited lung metastasis in a dose-dependant manner. In an in vitro cytotoxicity analysis, GAL at the concentration up to $500\;{\mu}g/ml$ did not affect the growth of B16-BL6 melanoma cells. In contrast, GAL showed the enhancement of splenocyte proliferating activity in a dose-dependent manner. Peritoneal macrophages stimulated with GAL produced various cytokines such as $1L-1{\beta},\;TNF-{\alpha},\;IFN-{\gamma}$ and IL-12. These data suggest that GAL has an antitumor activity to inhibit tumor metastasis, and its antitumor effects is associated with activation of nonspecific immnune related cells.

• Natural Product Sciences
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• 제17권2호
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• pp.135-141
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• 2011

Celastrus orbiculatus has been widely used as a traditional medicine for the treatment of many diseases including rheumatoid arthritis and odontalgia. In the present study, anti-metastatic activity of a methanolic extract from C. orbiculatus (MCO) was studied. A gelatin zymographic assay revealed that MCO has potent inhibitory effects on MMP-2 and MMP-9 activities in B16F10 melanoma cells. Moreover, MCO attenuated MMP expression via down-regulation of NF-${\kappa}$B translocation to the nucleus. Melanoma cell migration and invasion were also down-regulated by MCO. In addition, MCO significantly suppressed lung metastasis in an in vivo model. These results strongly suggest that MCO may possibly be used as a valuable anti-metastatic agent for cancer treatment.

• 동의생리병리학회지
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• 제25권6호
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• pp.968-974
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• 2011

Saussurea lappa Clarke is a well-known transitional medicine in Asia including Korea, China and Japan. It has been reported that Clarke has diverse effects such as anti-viral, anti-inflammatory, anti-cancer in human gastric cells and human prostate cancer cells. However, the anti-cancer effects and the mechanism of actions of Saussurea lappa Clarke are still unknown in breast cancer. In this study, we observed that Saussurea lappa Clarke inhibits the cell growth in a dose- and time-dependent manner in highly-metastatic MDA-MB-231 breast cancer cells. In order to examine whether Saussurea lappa Clarke suppresses cell growth inducing apoptosis cell death or cell cycle arrest, we analyzed DNA contents and cell cycle distribution using a flow cytometer and western blotting in MDA-MB-231 cells. We suggest that Saussurea lappa Clarke dose not induced apoptosis and induced G2/M phase cell cycle arrest. Moreover, Saussurea lappa Clarke also decreased the expression level of metastasis-angiogenesis releated protein such as VEGF. However, dose not changed the expression level of metastasis related protease MMP-1 in highly-metastatic MDA-MB-231 breast cancer cells. Therefore, Saussurea lappa Clarke might be good and useful chemotherapy agent highly-metastatic breast cancer patients.

• Journal of Acupuncture Research
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• 제20권5호
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• pp.159-171
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• 2003

Objective: To study on the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Asparagus cochinchinensis infusion solution. Methods: we put into Chung-wan(CV12) and Kwanwon(CV4) of C57bl/6 which are corresponding to human body with Asparagus coc hinchinensis infusion solution. We observed the effect on the expres sion of MMP-9. the expression of cytokine gene, number of pulmon ary colony, histological analysis on tissue metastasis of lung and liver. the expression of cytokine gene on PBMC. the number of $CD3e^+/CD4^+$. $CD3e^+/CD8^+$, $NK^+$ cell. Results: The results were obtained as follows I) The effect on expression of MMP-9. the expression of cytokine gen e was inhibited significantly in all the sample groups. compared with control group. 2) In pulmonary colony, sample groups were decreased significantly, compared with control group. especially, the group put into Chung-wan(CV12) was decreased significantly. 3) Histological analysis of sample groups inhibited significantly in all th e sample groups compared with that control groups in both of lung and liver. especially, the group put into Chung-wan(CV12) was inhibited significantly. 4) The effect on cytokine gene expression on PBMC of all the sample groups were increased significantly, compared with control group. 5) In flow cytometry, $CD3e^+/CD4^+$ $CD3e^+/CD8^+$, $NK^+$ cell in sample groups were increased compared with control group.

• International Journal of Oral Biology
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• 제42권3호
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• pp.107-115
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• 2017

Human malignant melanoma is an aggressive skin cancer which has been rising at a greater rate than any other cancers. Although various new therapeutic methods have been developed in previous studies, this disease has properties of high proliferation and metastasis rate which remain obstacles that have lead to a poor prognosis in patients. It has been reported that a specific Lactobacillus extract has anti-cancer and -metastasis effect in vitro and in vivo. However, previous research has not specified precisely what effect the Lactobacillus rhamnosus GG (LGG) extract has had on human malignant melanomas. In this study, we showed that the LGG extract has anti-cancer and -metastasis effects on the human malignant melanoma cell lines, A375P and A375SM. At first, it was found that, while the LGG extract affects human neonatal dermal fibroblasts slightly, it induced the dose-dependent anti-cancer effect on A375P and A375SM by a WST-1 proliferation assay. As a result of a real-time PCR analysis, the expression patterns of several genes related to cell cycle, proliferation, and apoptosis were modulating in a manner that inhibited the growth of both malignant melanoma cell lines after the treatment of the LGG extract. Furthermore, genes related to the epithelial-mesenchymal transition were down-regulated, and migration rates were also decreased significantly by the LGG extract. Our study showed that the LGG extract could be used as a potential therapeutic source.

• Journal of Microbiology and Biotechnology
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• 제16권12호
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• pp.1904-1911
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• 2006

The cell-free extracts of 250 yeasts were screened for their in vitro anti-angiogenic activity, to develop a new cancer metastasis inhibitor. Saccharomyces cerevisiae K-7 was selected as the producer of the anti-angiogenic agent, because it had the highest anti-angiogenic activity. The anti-angiogenic agent was produced maximally from hydrolysates of Saccharomyces cerevisiae K-7, when the yeast was cultured in yeast extract-peptone-dextrose medium at 30$^{\circ}C$ for 24 h, and cell-free extracts were than digested with pepsin for 4 h at 37$^{\circ}C$. The anti-angiogenic agent was further purified by ultrafiltration, Sephadex G-25 gel permeation chromatography and reverse-phase HPLC, and the anti-angiogenic activity of the final purified preparation was 72.7% at 10 $\mu$M/egg. The purified anti-angiogenic agent was found to originate from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) molecule of Saccharomyces cerevisiae K-7, and its peptide sequence was Val-Ser-Trp-Tyr-Asp-Asn-Glu-Tyr-Gly-Tyr-Ser-Thr-Arg-Val-Val-Asp. In the MTT assay, the shape of the HT-l 080 cell was clearly changed to a circular type at 0.2 mM purified anti-angiogenic agent. This result indicated that the growth of the HT-I080 cell was significantly inhibited at 0.2 mM of the purified anti-angiogenic agent. The MMP activity of the treated HT-l080 cells was not affected, evidenced by the gelatin zymography, indicating that the anti-angiogenic mechanism of the purified anti-angiogenic agent is not mediated through MMP activity.

• 한국식품영양학회지
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• 제20권3호
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• pp.253-258
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• 2007

In experimental lung metastasis of colon26-M3.1 carcinoma cells, we found that the prophylactic or therapeutic admini-stration of Inonotus obliquus extracts significantly inhibited lung metastasis. In an in vitro cytotoxicity analysis, the extracts did not affect colon26-M3.1 cell growth at concentrations up to 1000 ${\mu}g/m{\ell}$. Peritoneal macrophages that were stimulated with the extracts produced $TNF-{\alpha}$. These data suggest that Inonotus obliquus extract has antitumor activity to inhibit tumor metastasis, and its antitumor effects are partially associated with macrophages activation.