• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.213-221
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• 2017

Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.

• Journal of Ginseng Research
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• v.35 no.3
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• pp.315-324
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• 2011

This study investigated the effect of red ginseng extract on metastasis of colon cancer cells in vitro and in vivo. Wound healing migration, cell motility, invasion, and activity, protein expression, and mRNA expression of matrix metalloproteinases (MMPs) were examined in SW480 human colon cancer cells. SW480 cells were cultured with or without $100{\mu}g/L$ PMA in the absence or presence of various concentrations (100, 200, or $300{\mu}g/mL$) of red ginseng extract. Red ginseng extract treatment caused signifi cant suppression of cell motility and invasion (p<0.05) in SW480 cells. Red ginseng extract inhibited MMP-2 and MMP-9 activity and their protein and mRNA expression in a dose-dependent manner (p<0.05) in SW480 cells. For experimental metastasis, BALB/c mice were injected intravenously with CT-26 mouse colon cancer cells in the tail vein, and were orally administered various concentrations (0, 75, 150, or 300 mg/kg body weight) of red ginseng extract for 3 weeks. Numbers of pulmonary nodules were signifi cantly decreased in mice that were fed red ginseng extract (p<0.05). Plasma MMP-2 and MMP-9 activity signifi cantly decreased in response to treatment with red ginseng extract in mice (p<0.05). These data suggest that red ginseng extract may be useful for prevention of cancer invasion and metastasis through inhibition of MMP-2 and MMP-9 pathways.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.533-542
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• 2015

Little human tissue data are available for slow waves and migrating motor complexes, which are the main components of small bowel motility. We investigated the electrophysiological and mechanical characteristics of human ileal motility, in vitro. Ileum was obtained from patients undergoing bowel resection. Electrophysiological microelectrode recordings for membrane potential changes and mechanical tension recordings for contraction from smooth muscle strips and ileal segments were performed. Drugs affecting the enteric nervous system were applied to measure the changes in activity. Slow waves were detected with a frequency of 9~10/min. There were no cross-sectional differences in resting membrane potential (RMP), amplitude or frequency between outer and inner circular muscle (CM), suggesting that electrical activities could be effectively transmitted from outer to inner CM. The presence of the interstitial cell of Cajal (ICC) at the linia septa was verified by immunohistochemistry. Contractions of strips and segments occurred at a frequency of 3~4/min and 1~2/min, respectively. The frequency, amplitude and area under the curve were similar between CM and LM. In segments, contractions of CM were associated with LM, but propagation varied with antegrade and retrograde directions. Atropine, $N^W$-oxide-L-arginine, and sodium nitroprusside exhibited different effects on RMP and contractions. There were no cross-sectional differences with regard to the characteristics of slow waves in CM. The frequency of contractions in smooth muscle strips and ileal segments was lower than slow waves. The directions of propagation were diverse, indicating both mixing and transport functions of the ileum.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.165.2-165.2
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• 2003

Phosphatidylinositol 3-kinase (PI3K) and Rac play important roles that regulate cellular functions including cell survival and migration. In the present study, we investigated the functional roles of PI3K and Rac1 pathways in H-ras-induced invasive phenotype and motility of MCF10A cells. Akt, a downstream molecule of PI3K, was effectively activated not only by H-ras but also by N-ras, suggesting that the activation of PI3K pathway is not sufficient to induce metastatic potential of MCF10A cells. (omitted)

• Toxicological Research
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• v.30 no.4
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• pp.261-266
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• 2014

Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) have been implicated in cancer development and progression. However, the effects of PAHs on carcinogenesis are still poorly understood. Here, we characterized a mouse cancer cell line BNL 1ME A. 7R.1 (1MEA) derived by transformation of non-tumorigenic liver cell line BNL CL.2 (BNL) using 3-methylcholanthrene (3MC), a carcinogenic PAH. RT-PCR and immunoblot analysis were used to determine the expression level of mRNA and proteins, respectively. To determine functionality, cell motility was assessed in vitro using a transwell migration assay. Both mRNA and protein levels of E-cadherin were significantly decreased in 1MEA cells in comparison with BNL cells. While the expression levels of mesenchymal markers and related transcription factors were enhanced in 1MEA cells, which could lead to increase in cell motility. Indeed, we found that 7-day exposure of BNL cells to 3-MC reduced the level of the adhesion molecule and epithelial marker E-cadherin and increased reciprocally the level of the mesenchymal marker vimentin in a dose-dependent manner. Taken together, these results indicate that the process of epithelial-mesenchymal transition (EMT) may be activated during premalignant transformation induced by 3-MC. A mechanism study to elucidate the relation between 3-MC exposure and EMT is underway in our laboratory.

• BMB Reports
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• v.49 no.11
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• pp.623-628
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• 2016

GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly expressed in human brain tissues. Currently, the function of GPR78 is unknown. This study revealed that GPR78 was expressed in lung cancer cells and functioned as a novel regulator of lung cancer cell migration and metastasis. We found that knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover, GPR78 modulated the formation of actin stress fibers in A549 cells, in a RhoA- and Rac1-dependent manner. At the molecular level, GPR78 regulated cell motility through the activation of $G{\alpha}q$-RhoA/Rac1 pathway. We further demonstrated that in vivo, the knockdown of GPR78 inhibited lung cancer cell metastasis. These findings suggest that GPR78 is a novel regulator for lung cancer metastasis and may serve as a potential drug target against metastatic human lung cancer.

• BMB Reports
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• v.51 no.3
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• pp.157-162
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• 2018

Angiogenesis is a complex, multistep process involving dynamic changes in endothelial cell (EC) shapes and behaviors, especially in specialized cell types such as tip cells (with active filopodial extensions), stalk cells (with less motility) and phalanx cells (with stable junction connections). The Hippo-Yes-associated protein (YAP)/ transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in development, regeneration and organ size by regulating cell-cell contact and actin cytoskeleton dynamics. Recently, with the finding that YAP is expressed in the front edge of the developing retinal vessels, Hippo-YAP/TAZ signaling has emerged as a new pathway for blood vessel development. Intriguingly, the LATS1/2-mediated angiomotin (AMOT) family and YAP/TAZ activities contribute to EC shapes and behaviors by spatiotemporally modulating actin cytoskeleton dynamics and EC junction stability. Herein, we summarize the recent understanding of the role of Hippo-YAP/TAZ signaling in the processes of EC sprouting and junction maturation in angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6007-6012
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• 2013

ANXA2, a member of the annexin family, is overexpressed and plays important roles in tumor development. However, the significance of ANXA2 expression in gastric carcinoma has not been clarified.To elucidate its roles in growth of gastric cancer, ANXA2 expression in SGC-7901 cells was inhibited with a designated siRNA, then cell proliferation, cell cycling, apoptosis and motility were determined by MTT assay, flow cytometry, Hoechst 33342 staining and wound healing assay, respectively. To further assess the behavior of ANXA2 deleted SGC-7901 cells, changes of microstructures were observed under fluorescence microscopy, laser scanning confocal microscopy and electron microscopy. We found that inhibition of ANXA2 expression caused cell proliferation to decrease significantly with G1 arrest, motility to be reduced with changes in pseudopodia/filopodia structure and F-actin and ${\beta}$-tubulin expression, and apoptosis to be enhanced albeit without significance. At the same time, ANXA2 deletion resulted in fewer pseudopodia/filopodia, non-stained areas were increased, contact inhibition among cells reappeared, and expression of F-actin and ${\beta}$-tubulin was decreased, with induction of polymerized disassembled forms. Taken together, these data suggest that ANXA2 overexpression is important to maintain the malignancy of cancer cells, and this member of the annexin family has potential to be considered as a target for the gene therapy of gastric carcinoma.

• Journal of Advanced Information Technology and Convergence
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• v.9 no.1
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• pp.103-113
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• 2019

Motivation: Polymerized actin-based cytoskeletal structures are crucial in shape, dynamics, and resilience of a cell. For example, dynamical actin-containing ruffles are located at leading edges of cells and have a significant impact on cell motility. Other filamentous actin (F-actin) bundles, called stress fibers, are essential in cell attachment and detachment. For this reason, their mechanistic understanding provides crucial information to solve practical problems related to cell interactions with materials in tissue engineering. Detecting and counting actin-based structures in a cellular ensemble is a fundamental first step. In this research, we suggest a new method to characterize F-actin wrapping fibers from confocal fluorescence image stacks. As fluorescently labeled F-actin often envelope the fibers, we first propose to segment these fibers by diminishing an energy based on maximum flow and minimum cut algorithm. The actual actin is detected through the use of bilateral filtering followed by a thresholding step. Later, concave actin bundles are detected through a graph-based procedure that actually determines if the considered actin filament is enclosing the fiber.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.3
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• pp.178-184
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• 2002

High-throughput screening has become a popular method used to identify new “leads”for potentially therapeutic compounds. Further screening of these lead compounds is typically done with secondary assays which may utilize living, functioning cells as screening tools. A problem (or benefit) with these cell-based assays is that living cells are very sensitive to their environment. We have been interested in the process of stem cell migration and how it relates to the cellular therapy of bone marrow transplantation. In this study we describe a secondary, cell-based assay for screening the effects of various in-vitro conditions on Immature Hematopoietic Cell (IHC) migration. Our results have revealed many subtle factors, such as the cell's adhesive characteristics, or the effect of a culture's growth phase, that need to be accounted for in a screening protocol. Finally, we show that exponentially glowing KG1a cells (a human IHC cell line) were 10 times more motile than those in the lag or stationary phases. These data strongly suggest that KG1a cells secrete a chemokinetic factor during the exponential growth phase of a culture.