• 대한생식의학회:학술대회논문집
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• 2004.06a
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• pp.92.2-93
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• 2004

• Journal of Life Science
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• v.19 no.9
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• pp.1200-1208
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• 2009

Tight junctions (TJs) that act as paracellular permeability barriers play an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. In this study, we investigated the correlation between the tightening of TJs, permeability and the invasive activity of genistein - a bioactive isoflavone of soybeans - in human breast carcinoma MCF-7 and MDA-MB-231 cells. The inhibitory effects of genistein on cell proliferation, motility and invasiveness were found to be associated with the increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. Additionally, the immunoblotting results indicated that genistein repressed the levels of the proteins that comprise the major components of TJ, claudin-3 and claudin-4, which play a key role in the control and selectivity of paracellular transport. Furthermore, genistein decreased the metastasis-related gene expressions of insulin like growth factor-1 receptor and snail, while concurrently increasing that of thrombospondin-1 and E-cadherin. In addition, we demonstrated that claudins play an important role in the anti-motility and invasiveness of genistein using claudin-3 small interfering RNA. Taken together, our results indicate a possible role for genistein as an inhibitor of cancer cell invasion through the tightening of TJs, which may counteract the up-regulation of claudins. In addition, our results indicate that this may be beneficial for the inhibition of tumor metastasis.

• The Journal of Pediatrics of Korean Medicine
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• v.37 no.4
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• pp.25-33
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• 2023

Objective This study aimed to confirm the effect of Sabaek-san extract on the recovery of skin damage in atopic dermatitis-induced mice. Methods In this study, we used 4-week-old NC/Nga mice that were assigned to four groups: control (Ctrl), lipid barrier elimination (LBEG), dexamethasone (Dx) administration after lipid barrier elimination (DxAG), and Sabaek-san extract administration after lipid barrier elimination (SBAG). Ten rats were assigned to each treatment group. After drug administration for 3 days following lipid barrier elimination, ceramide kinase, caspase 14, sodium hydrogen antiporter (NHE), cathelicidin, claudin, and Toll-like receptor (TLR2) were observed to confirm restoration of skin moisturizer production, antimicrobial barriers, and tight junctions in the skin barrier. Results Ceramide kinase and caspase 14 positive reactions were significantly higher in the SBAG group than in the LBEG or DxAG groups. NHE and cathelicidin showed a higher positive reaction in the SBAG group than in the LBEG and DxAG groups. Claudins and TLR2 showed a higher positive reaction in the SBAG group than in the LBEG or DxAG groups. Conclusion It was confirmed that Sabaek-san extract may have the potential to restore damaged skin barrier in atopic dermatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4387-4392
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• 2015

Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well-known adhesion effect.

• Korean Journal of Plant Resources
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• v.36 no.3
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• pp.207-218
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• 2023

Hepatocellular carcinoma (HCC) has a poor prognosis and high metastasis and recurrence rates. Although extracts of Alnus hirsuta (Turcz. ex Spach) Rupr. (AH) have been demonstrated to possess potential anti-inflammatory and anti-cancer activities, the underlying mechanism of AH in HCC treatment remains to be elucidated. We investigated the effects and potential mechanisms of AH on migration and invasion of Hep3B cells. Within the non-cytotoxic concentration range, AH significantly inhibited motility and invasiveness of Hep3B cells in a concentration-dependent manner. Inhibitory effects of AH on cell invasiveness are associated with tightening of tight junctions (TJs), as demonstrated by an increase in transepithelial electrical resistance. Immunoblotting indicated that AH decreased levels of claudins, which form major components of TJs and play key roles in the control and selectivity of paracellular transport. Furthermore, AH inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in Hep3B cells. Therefore, AH inhibits migration and invasion of Hep3B cells by inhibiting the activity of MMPs and tightening TJs through suppression of claudin expression, possibly by suppressing the PI3K/AKT signaling pathway.

• Journal of Life Science
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• v.17 no.9 s.89
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• pp.1298-1302
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• 2007

A hallmark of cancers is 'leaky' tight junctions (Tjs). TJs mediated paracellular permeability is elevated and TJs maintained cell polarity is frequently lost. Concomitantly, TJs-associated proteins including members of the claudin family of proteins are dysregulated. Recent findings indicate that these TJs changes can contribute to cancer progression. In this study, we examined the effects of ${\beta}-lapachone$, a quinone compound obtained from the bark of the lapacho tree (Tabebuia avellanedae), on the Tjs-associated regulators in human hepatocarcinoma cell lines, HepG2 and Hep3B. ${\beta}-lapachone$ treatment downregulated the levels of insulin-like growth factor 1 receptor (IGF-lR) proteins in both HepG2 and Hep3B cells. But the levels of claudin-3 and -4 proteins were increased in ${\beta}-lapachone$-treated HepG2 and Hep3B cells. And also the zonnula occludens-l (la-I) and p-catenin protein levels by ${\beta}-lapachone$ were increased in a time-dependent manner. However, claudin-3 and -4 mRNA levels were uninhibited by ${\beta}-lapachone$ in HepG2 and Hep3B. The present results suggest that the upregulation of claudin-3 and -4 protein levels by ${\beta}-lapachone$ occurs by a post-transcriptional mechanism and points to a novel mechanism by ${\beta}-lapachone$.