• 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.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.177-177
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• 2003

Tumor cell invasion and metastasis are a complex multistep process that involves the degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs). Tissue inhibitor of metalloproteinase-1 (TIMP-1) acts as a negative regulator of matrix metalloproteinase and thus prevents tumor cell invasion and metastasis by preserving extracellular matrix integrity.(omitted)

• Food Science and Preservation
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• v.16 no.4
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• pp.599-603
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• 2009

To evaluate the anti-tumor activity of Flammulina velutipes extract, we used an in vitro wound-healing assay, and an in vivo approach using a mouse melanoma model. Wound-healing activity in B16 cells was affected by the extract in a dose-dependent manner, indicating that the extract had anti-metastatic activity. The extract also exhibited strong anti-tumor activity against lung cancer when B16 cells were injected into mouse veins together with B16 melanoma cells. The results indicatethat the Flammulina velutipes extract decreased B16 cancer cell growth by inhibition of cell migration both in vitro and in vivo.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.521-525
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• 2014

BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through $H_2DCF$-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT ($10{\mu}M$ and $30{\mu}M$) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT ($10{\mu}M$ and $30{\mu}M$) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.

• The Journal of Internal Korean Medicine
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• v.34 no.1
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• pp.31-45
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• 2013

Objectives : Gokgisaeng (Korean mistletoe) is used for the treatment of inflammatory and cancer diseases in traditional Korean medicine and its major component lectins have been reported to induce nitric oxide (NO) in RAW 264.7 macrophages, and also induce apoptosis of various types of cancer cells, although its modulatory effects on cancer cell migration and macrophage activation is poorly understood. The aim of this study is to clarify molecular mechanisms of action responsible for the anti-inflammatory and antitumor migration potentials of Korean mistletoe extract (KME). Methods : We investigated the anti-inflammatory activity of KME on NO production and inducible nitric oxide synthase (iNOS) expression by lipopolysaccharide (LPS) in both RAW 264.7 macrophages and rat C6 glioma cells, and also evaluated inhibitory efficacy on glioma cell growth and migration. For assessment, XTT assay, nitrite assay, RT-PCR, scratch-wound and Boyden chamber assay, and western blot analysis were performed. Results : Previously reported, unlike the efficacy of Gokgisaeng lectin, KME inhibited NO production and iNOS expression, and suppressed pro-inflammatory mediators including IL-$1{\beta}$, IL-6, COX-2, iNOS in LPS-stimulated RAW 264.7 cells. Furthermore, KME suppressed tumor cell growth and migration, and it also inhibited LPS-induced NO release and iNOS activation by down-regulating expression of protein kinase C (PKC) and phosphorylation of ERK in C6 glioma cells. Conclusions : Our research findings provide evidence that KME can play a significant role in blocking pro-inflammatory reaction and malignant progression of tumors through the suppression of NO/iNOS by down-regulating of inflammatory signaling pathways, PKC/ERK.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.323-328
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• 2017

Angiogenesis is a process including members of the angiogenic factors. In particular, fibroblast growth factor 2 (FGF2) is considered the most potent angiogenic factor because it promotes cell proliferation and tube formation. A recent study reported that fucoidan derived from marine plant potentiated FGF-2 induced tube formation in human endothelial cells. On the other hand, the molecular mechanisms involved in the angiogenic activity of fucoidan and FGF2 are unknown. In this study, a fucoidan treatment promoted angiogenesis induced by FGF2. The effects of fucoidan on FGF2-induced angiogenesis were confirmed by a proliferation assay using a CellTiter96 Aqueous One solution after a treatment with fucoidan and FGF2. The tube formation and wound healing assay for the angiogenic activity were also confirmed. Reverse transcription PCR showed a change in the mRNA of vascular endothelial growth factor-A (VEGF-A), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase9 (MMP9), and the signal transducer and activator of transcription3 (STAT3). In summary, the Fucoidan/FGF2 treatment induced an increase in cell proliferation, improved the tube formation and wound healing activity, and altered the STAT3, VEGF-A, ICAM-1, and MMP9 mRNA expression levels. Further research will be needed to provide a scientific explanation in terms of cell-signaling and confirm the present findings.

• Oncology Letters
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• v.18 no.2
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• pp.1189-1198
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• 2019

Prostate cancer (PC) metastasizes to the bone, and a small number of cancer cells, described as cancer stem cells (CSCs), have the ability to differentiate into tumor cells. CSCs are responsible for tumor recurrence and metastases. In the present study, we examined whether ectopic overexpression of CD133, a key molecule maintaining the stability of CSCs in the human PC cell line, LnCaP, caused bone metastasis in a mouse model. Ectopic overexpression of CD133 was induced in LnCaP cells, and CSC-related protein expression was measured. Furthermore, a colony-forming assay was performed to compare results against the blank green fluorescent protein-expressing cells. Furthermore, epithelial to mesenchymal transition-related protein expression, cell migration and wound healing were investigated. To assess the role of CD133 in bone metastasis, CD133-overexpressing LnCaP cells were inoculated into mice via intracardiac injection, and bone metastasis was assessed via histological and immunohistochemical study. In addition, cytokine arrays were used to determine the cytokines involved in bone metastasis. Ectopic overexpression of CD133 in LnCaP cells increased CSC properties such as Oct-4 and Nanog expression and colony-forming ability. Furthermore, epithelial-to-mesenchymal transition (EMT) properties, including decreased E-cadherin and increased vimentin expression, wound gap distance, and cell migration increased. CD133 overexpression led to formation of bone metastatic tumors in mice, consistent with results of hematoxylin and eosin staining. In addition, an increase in expression of the macrophage-migration inhibitory factor was observed at the tumor margin in mice inoculated with CD133+ LNCaP cells. These findings suggest a regulatory role of CD133 in stem cell and EMT properties, and the sustained acquisition of osteolytic features in PC. Therefore, our results may facilitate development of a novel classification system and therapeutic strategies for bone metastasis of PC.

• Natural Product Sciences
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• v.23 no.4
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• pp.286-290
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• 2017

Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are highly dangerous nosocomial pathogens, cause the symptoms of skin infections, pressure sores, sepsis, blood stream and wound infections. Unfortunately, these pathogens are immune to the most common antibiotics, such as, carbapenem, aminoglycoside and fluoroquinolone. Therefore, it is imperative that new and effective antibiotics be developed. In the present study, the antimicrobial effects of Aloe vera MAP (modified Aloe polysaccharide) on Staphylococcus aureus and Bacillus subtilis, Escherichia coli and Enterobacter aerogenes, and clinical Pseudomonas aeruginosa and clinical Acinetobacter baumannii were comprehensibly investigated. Prior to the growth inhibition effect measurement and antibiotic disc diffusion assay on gram-positive and gram-negative bacteria and selected multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, antimicrobial resistance screening was performed for the multidrug-resistant bacteria obtained from clinical isolates. The results for showed the Aloe vera MAP had a concentration-dependent effect on all of examined bacteria, particularly on Pseudomonas aeruginosa. Anti-inflammatory and anti-oxidant experiments were also performed dose dependently effects to confirm the beneficial physiological effects of Aloe vera MAP.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.9
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• pp.5628-5636
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• 2014

Currently, many countries have an interest in developing cosmetics materials using native plants. In this aspect, there is increasing need to develop cosmetics materials using native plants in our county. In the present study, calluses were induced from Artemisia annua Linne, which was highlighted because of its useful effects, such as anti-cancer, anti-fungal and anti-inflammation. Water and ethanol extractions were performed from the calluses of Artemisia annua Linne. After the mass production of Artemisia annua Linne's calluses, water and ethanol extraction was performed to examine its functional roles in healing wounds and inflammation. The differences in the effective elements were observed in the ethanol extract. The callus showed anti-inflammation activity through the suppression of the inflammation-related gene, COX-2, and ethanol extracts showed their ability to heal wounds. Overall, these results suggest that the extract of Artemisia annua Linne's calluses is a natural and environment-friendly material, and can be used as medical supplies associated with anti-inflammation and healing wounds.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.8
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• pp.5070-5077
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• 2014

Many countries in the world have protected their native plants and utilized them as industrial materials in each country. In this aspect, it is increasingly important to develop cosmetics materials using native plants in Korea. Cosmetic materials have been developed with niche plants, such as Campanula takesimana Nakai, Dianthus superbus, Aster spathulifolius in Ullengdo, in which a specific plant distribution by distinct climate and environment was present. Water and ethanol extractions were performed from the calluses of Campanula takesimana Nakai, Dianthus superbus, Aster spathulifolius. HPLC analysis revealed different compositions and functions of effective elements in each ethanol extract. For example, all types of ethanol extracts showed an ability to heal wounds. In particular, the expression of the inflammation-related gene, COX-2, was decreased in response to the ethanol extracts of Dianthus superbus. These results indicate that the ethanol extracts from niche plants' calluses in Ullengdo are natural and environmentally-friendly compounds, and can be used as medical supplies associated with anti-inflammation and wound healing.