• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1011-1015
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• 2005

Antitumor and anti-metastatic effects of mineral powder(MP) were studied. In the present study, MP did not exhibit the any cytotoxic activity against leukemic cells such as L1210 and U937 tumor cell lines in vitro. Also, MP did not exhibit the any cytotoxic activity against solid cells such as A549 and B16-BL6 tumor cell lines in vitro. However, in vivo, MP exhibit a significant antitumor activity in BDF1 mice bearing Lewis lung carcinoma cells(LLC) with inhibition rates of 46 and $23\%$ at 200 and 100 mg/kg/day, respectively. Furthermore, in pulmonary colonization assay, MP exhibit the inhibitory effect of tumor metastasis. From these results, it was concluded that MP had antitumor and anti-metastatic activity suggesting its application for the prevention and treatment of cancer.

• Archives of Pharmacal Research
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• v.20 no.6
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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.

• Molecular Medicine Reports
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• v.21 no.3
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• pp.1374-1382
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• 2020

Arctigenin is a natural lignan that is found in burdock with anti-viral, -oxidative, -inflammatory and anti-tumor activities. In the current study, the effect of arctigenin on metastatic potential was examined in 4T-1 mouse triple-negative breast cancer cells. The results indicated that arctigenin inhibited cell motility and invasiveness, which was determined using wound healing and transwell invasion assays. Arctigenin suppressed matrix metalloprotease-9 (MMP-9) activity via gelatin zymography, and protein expression of cyclooxygenase-2 (COX-2) and MMP-3. Furthermore, arctigenin attenuated the mRNA expression of metastatic factors, including MMP-9, MMP-3 and COX-2. Based on these results, the effect of arctigenin on the mitogen-activated protein kinase (MAPK)/activating protein-1 (AP-1) signaling pathway was assessed in an attempt to identify the regulatory mechanism responsible for its anti-metastatic effects. Arctigenin was demonstrated to inhibit the phosphorylation of extracellular signal-regulated protein kinase (ERK) and c-Jun N- terminal kinase (JNK), and the nuclear translocations of the AP-1 subunits, c-Jun and c-Fos. In summary, the present study demonstrated that in 4T-1 mouse triple-negative breast cancer cells the anti-metastatic effect of arctigenin is mediated by the inhibition of MMP-9 activity and by the inhibition of the metastasis-enhancing factors MMP-9, MMP-3 and COX-2, due to the suppression of the MAPK/AP-1 signaling pathway. The results of the current study demonstrated that arctigenin exhibits a potential for preventing cell migration and invasion in triple negative breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3071-3075
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• 2016

Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting anti-oxidant, anti-inflammatory and anti-carcinogenic effects. Here, we investigated the anti-cancer activity of morin focusing on anti-adhesive influence. We performed experiments with MDA-MB-231 human breast cancer cells. Morin inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM-1 on MDA-MB-231 cells as well as HUVECs. Morin also decreased the expression of N-cadherin on MDA-MB-231 cells. In addition, there was apparent anti-metastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM-1, and EMT by targeting N-cadherin, and that it features anti-metastatic activity in vivo. Further investigation of possible anti-metastatic activity of morin against human breast cancer cells is warranted.

• Korean Journal of Pharmacognosy
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• v.31 no.4
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• pp.394-400
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• 2000

Tumor cell interaction with the extracellular matrix (ECM) is defined as the critical event of tumor invasion that signals the initiation of a metastatic cascade. To search for anti-metastatic agent from plants, several plant extracts were screened by cell- ECM anti-adhesion test. As result, Boehmeria pannosa, Dryopteris crassirhizoma, Scilla scilloides, and Agrimonia pilosa were shown a significant anti-adhesion activity.

• Molecules and Cells
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• v.39 no.5
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• pp.403-409
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• 2016

NME1 is a well-known metastasis suppressor which has been reported to be downregulated in some highly aggressive cancer cells. Although most studies have focused on NME1, the NME1 gene also encodes the protein (NME1L) containing N-terminal 25 extra amino acids by alternative splicing. According to previous studies, NME1L has potent anti-metastatic activity, in comparison with NME1, by interacting with $IKK{\beta}$ and regulating its activity. In the present study, we tried to define the role of the N-terminal 25 amino acids of NME1L in $NF-{\kappa}B$ activation signaling. Unfortunately, the sequence itself did not interact with $IKK{\beta}$, suggesting that it may be not enough to constitute the functional structure. Further construction of NME1L fragments and biochemical analysis revealed that N-terminal 84 residues constitute minimal structure for homodimerization, $IKK{\beta}$ interaction and regulation of $NF-{\kappa}B$ signaling. The inhibitory effect of the fragment on cancer cell migration and $NF-{\kappa}B$-stimulated gene expression was equivalent to that of whole NME1L. The data suggest that the N-terminal 84 residues may be a core region for the anti-metastatic activity of NME1L. Based on this result, further structural analysis of the binding between NME1L and $IKK{\beta}$ may help in understanding the anti-metastatic activity of NME1L and provide direction to NME1L and $IKK{\beta}$-related anti-cancer drug design.

• Natural Product Sciences
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• v.17 no.2
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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.

• Korean Journal of Pharmacognosy
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• v.35 no.2 s.137
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• pp.110-115
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• 2004

For the evaluation of anti-tumor activity of Korean Oldenlandia Herb (KOH) and Radix (KOR), our experiment was performed with methanol extracts of KOH and KOR. They did not shown any cytotoxicity against HT1080 cell lines. However, they effectively showed anti-metastatic activity through inhibition of the adhesion of HT1080 cells to gelatin, downregulated the expression of MMP2 and uPA and upregulated the expression of TIMP2. They also inhibited tube formation of HUVECs induced by bFGF. However, they did not affect DNA topoisomerase I activity. Simiarly, the T/Cs % in KOH and KOR treated mice were increased 134.9% and 171 %, respectively at 2500 mg/kg. These results suggest that KOH and KOR exert anti-tumor activity via anti-metastatic and anti-angiogenic activities. The further study for isolation of effective compounds and its exact mechanism and comparative study with Chinese Oldenlandia Herba will be required.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.3
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• pp.59-67
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• 2023

Purpose : Epithelial-to-mesenchymal transition (EMT) is recognized as an important cellular response in metastatic proceduresand characterized by loss of cellular polarity as well as gain of mesenchymal features, which enables migration and invasion. Hepatocellular carcinoma (HCC) is one of the most common primary carcinomas in the liver and exhibits a poor prognosis due to frequent extrahepatic metastasis. Taraxacum officinale has been used for a long time in oriental medicine because of its various pharmacological activitiessuch as anti-rheumatic, anti-inflammatory, antioxidative, and anticarcinogenic activities. In this study, the anti-metastatic activity of T. officinale water extract (TOWE) and ethanol extract (TOEE) was investigated through the regulation of EMT in the Huh7 cells. Methods : The effects of TOWE and TOEE on migratory and invasive activities were investigated by wound healing and in vitro invasion assays. Western blot analysis was also applied to analyze protein expression levels associated with EMT and their upstream transcription factors in Huh7 cells. Results : TOWE and TOEE treatment potently inhibited migration and invasion of Huh7 cells compared to the untreated group. Both extracts treatment inhibited protein expression levels of N-cadherin, matrix metalloproteinase (MMP)-9, and vimentin while E-cadherin was significantly accelerated. In addition, the activated status of transcription factors, Snail, nuclear factor (NF)-κ B, and zinc finger E-box binding homeobox (ZEB)1 was also inhibited with statistical significance. In comparison to both extracts, TOEE more potently attenuated migration, invasion, and EMT markers as well as their transcription factors in Huh7 cells than TOWE, which means that TOEE might possess more functional phytochemicals than TOWE. Conclusion : Consequently, TOWE and TOEEattenuated metastatic activity of hepatocellular carcinoma through the regulation of EMT markers and their transcription factors in Huh7 cells, which means that T. officinale might be a promising strategy for a chemopreventive agent against HCC metastasis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1470-1474
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• 2008

This study was performed to examine the anti-metastatic effect of ethanol extract of Samguikoeui-Tang (SGKE), a formula consisting of four oriental herbs, in highly-metastatic HT1080 human fibrosarcoma cells. SGKE significantly inhibited the adhesion of HT1080 cells to matrigel at nontoxic concentrations in a dose-dependent manner, while it did not exert cytotoxicity against HT1080 cells up to the concentration of 100 ${\mu}g$/ml. Also, SGKE depressed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography. However, SGKE did not affect the mRNA expression of MMP-2 and TIMP-2, an inhibitor of MMP-2, by RT-PCR analysis. In addition, the effect of SGKE on HT1080 cell invasion was determined using Boyden chamber assay. SGKE suppressed the invasion of HT1080 cells in a dose-dependent manner. Taken together, these results suggest that SGKE has an anti-metastatic effect via inhibition of MMP-2 and -9 activities.