The root of Paeonia lactiflora has been used in Chinese medicine. We conducted to check the comparative qualities of ethanol solvent extraction (PLE) and supercritical carbon dioxide extraction (PLS) of P. lactiflora root. PLE had higher antioxidant and polyphenol contents than PLS. But, PLS were significantly increased peroxisome proliferator-activated receptor (PPAR)-α. In addition, PLS inhibited the adipocyte differentiation of 3T3-L1 cells. When treated with the extract at a concentration of 100 μg/mL, the Wnt/β-catenin pathway reporter luciferase activity of HEK 293-TOP cells increased approximately by 3-folds compared to that of the untreated control group. These results indicate that P. lactiflora supercritical carbon dioxide extract may serve as a cosmeceutical for improving skin barrier function and the treatment of obesity.
A nineteen years old male patient showed a cystic lesion in left maxillary canine to premolar area (#23-#25). This lesion was asymptomatic, and found during his routine radiological check in local clinic. In the radiological observation the cystic lesion showed round radiolucent image containing many calcified bodies which were usually small but irregular in shape, expanding tumorously and resulted in the displacement of canine and second premolar in the absence of first premolar. The lesion was surgically enucleated, and a cystic fibrous tissue containing abnormal teeth was removed and examined pathologically. With the histological observation of tumorous odontogenic epithelium including many ghost cells, which were closely associated with abortive teeth, the lesion was finally diagnosed as CCOT associated with complex odontoma. The ghost cells of CCOT was strongly positive for β-catenin, GADD45, and LC3, and slightly positive for MMP-9, while they were rarely positive for BCL2, Wnt1, HSP-70, and p38. Therefore, it was presumed that the ghost cells of CCOT might undergo dormant cell state through altered cytodifferentiation stimulated by severe growth arrest, DNA damage signaling, and abundant autophage formation.
Proteinuric conditions demonstrate structural and compositional changes of the foot processes and slit diaphragms between podocytes. β-Catenin in podocytes serves as an adapter protein anchoring P-cadherin of slit diaphragms to actin filaments of the podocyte cytoskeleton. To investigate the effect of ginseng total saponin (GTS) on pathologic changes of podocyte P-cadherin/β-catenin unit induced by diabetic conditions, we cultured mouse podocytes under: 1) normal glucose (5 mM, = control); 2) high glucose (HG, 30 mM); 3) advanced glycosylation end products (AGE)-added; or 4) HG plus AGE-added conditions and treated with GTS. In confocal imaging, β-catenin colocalized with P-cadherin predominantly at intercellular junction area. However, diabetic conditions relocalized and concentrated both molecules at perinuclear cytoplasmic area. In Western blotting, diabetic conditions, especially HG plus AGE-added condition, also decreased cellular β-catenin protein levels at 6, 24, and 48 hours. GTS improved such quantitative and qualitative changes of β-catenin. These findings imply that HG plus AGE have an influence on the redistribution and amount of P-cadherin/ β-catenin unit of podocytes, which can be reversed by GTS.
Oral lichen planus (OLP) is an atypically keratinized and ulcerative lesion, producing severe pain and discomforts in the involved patients. Nevertheless, the etiological factor or the pathogenetic mechanism has not been clearly elucidated. In the present study, the different gene expressions were screened in 21 cases of OLP by immunohistochemical (IHC) array method using 80 antibodies, and found that the pathway of E-cadherin/β-catenin was abnormally expressed compared to the other essential genetic pathways. Particularly, the expressions of eIF5A, DHS, and DOHH, which are the biomarkers of protein translation, were remarkably reduced, nevertheless the expression of β-catenin was strongly positive in the 7 cases among 21 cases of OLP. The other expressions of p53, BCL-2, MDM-2, PAKT, BAX, BAK, BAD, NFkB, HO-1, etc, were usually weak or sparse, while the expressions of PCNA, CDK4, and HSP-70 were markedly increased. Taken together, it is presumed that the overexpression of β-catenin indicates the derangement of E-cad/β-catenin/NFkB pathway, causing the transcription of cellular proliferating genes in downstream events, i.e., PCNA and CDK4, and that it may be eventually relevant to the malignant potential of OLP epithelial cells. It is also suggested that the activation of β-catenin/TCF/LEF1 pathway be closely relevant to the immunological reaction of OLP with the accumulation of T-cells underneath the mucosal epithelium.
Recurrence-metastasis status of squamous cell carcinoma of tongue is a challenging oncologic problem. This study examined the expression of E-cadherin/β-catenin cell adhesion complex in squamous cell carcinoma of the tongue through an immunohistochemical study. Twenty samples from 15 patients with squamous cell carcinoma of the tongue, who were treated at the Department of Oral and Maxillofacial Surgery, consisted of primary or recurrent tumors along with matched metastatic lymph nodes were retrieved for immunohistochemical staining and grouped based on recurrence-metastasis status.Differences in stain localization were noted in E-cadherin, β–catenin and phospho β–catenin staining between different tumor groups based on the recurrence-metastasis status. The number of phospho β-catenin stain positive cells was found to have a significant role in survival. E-cadherin confirms its role as a powerful individual differentiation indicator and the role of β-catenin specially the phospho type elicts interest
Periodontal ligament (PDL) tissue is a connective tissue that is interposed between the roots of the teeth and the inner wall of the alveolar bone socket. PDL is always exposed to physiologic mechanical force such as masticatory force and PDL cells play important roles during orthodontic tooth movement by synthesizing and secreting different mediators involved in bone remodeling. The Wnt/β-catenin signaling pathway was recently shown to play a significant role in the control of bone formation. In the present study, we applied cyclic tensile stress of 20% elongation to cultured human PDL cells and assessed its impact after six days upon components of the Wnt/β-catenin signaling pathway. RTPCR analysis showed that Wnt1a, Wnt3a, Wnt10b and the Wnt receptor LRP5 were down-regulated, whereas the Wnt inhibitor DKK1 was up-regulated in response to these stress conditions. In contrast, little change was detected in the mRNA expression of Wnt5a, Wnt7b, Fz1, and LRP6. By western blotting we found decreased expression of the β-catenin and p-GSK-3β proteins. Our results thus show that mechanical stress suppresses the canonical Wnt/β-catenin signaling pathway in PDL cells.
β-catenin is a cytoplasmic protein that participates in the assembly of cell-cell adherens junctions by binding cadherins to the cytoskeleton. In addition, it is a key component of the Wnt signaling pathway. Activation of this pathway triggers the accumulation of β-catenin in the nucleus, where it activates the transcription of target genes. Abnarmal accumulation of β -catenin is characteristic of polyposis coli(APC) or Axin tumor suppressor proteins, which regulates β-catenin degradation, or activating mutations in β-catenin molecule itself. Here we show that overexpression of Sox4 down-regulates wild type β-catenin in HEK 293 cells. The inhibitory effect of Sox4 on wild type β-catenin is apparently mediated by the ubiquitin- proteasoem system and requires an active glycogen synthase kinase 3β(GSK3β). Mutations in the N-terminus of β -catenin(S33Y) which compromise its degradation by the proteasomes or inhibition of GSK3β activity rendered β-catenin resistant to down-regulation by Sox4. In light of recent evidence that Sox4 expression is activated in colon and other tumors with β-catenin dysregulation, our findings suggest that Sox4 is part of a feedback inhibitory pathway for Wnt signaling in normal cells. Moreover, the mutations in APC, Axin or β-catenin in cancer cells appear to render β-catenin resistant to the effects of Sox4 inhibition.
Odontogenic ghost cell tumor (OGCT) is considered as a neoplastic counterpart of the calcifying odontogenic cyst (COC). β-catenin mutations have been described in COC suggesting a critical role in its histogenesis. In this study, we report a patient with OGCT contains a missense mutation on codon 3 (ACT -> TCT). Immunohistochemistry showed nuclear, cytoplasmic, and membranous accumulation of β-catenin in the tumor cells. TUNEL assay showed positive signals in nucleated cells adjacent to the ghost cells. Our data suggest that β-catenin plays an important role in the tumorigenesis of OGCT. OGCT may developed by improper differentiation process coordinated by WNT signaling pathway. Further studies are needed to determine a genotypic/phenotypic characteristics of ghost cell containing odontogenic lesions.
이상의 연구 결과로 미루어 볼 때, 도깨비부채 잎(RPL)은 β -catenin의 분해 유도를 통해 대장암, 유방암, 폐암, 전립선암 및 췌장암 세포의 생육을 억제하는 것으로 나타났다. 본 결과는 도깨비부채 잎의 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다. 그러나 추가적 연구를 통해 도깨비 부채 잎의 항암 활성물질의 분석연구가 필요할 것으로 사료된다.
In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on β-catenin level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased β-catenin level in both protein and mRNA level. MG132 decreased the downregulation of β-catenin protein level induced by STB and STL. However, the inhibition of GSK3β by LiCl or ROS scavenging by NAC did not block the reduction of β-catenin protein by STB and STL. Our results suggested that STB and STL may downregulate β-catenin protein level independent on GSK3β and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.
The Wnt/β-catenin signaling pathway is mandatory in adipogenesis. In this study, we investigated the applicability of functional materials for the treatment of obesity by examining Wnt/β-catenin pathway reporter activity related to adipocyte differentiation inhibiting with korean native plant extracts. The luciferase activity of HEK 293-TOP cells increased the reporter activity approximately 152% and 130% by treatment with Sanguisorba officinalis and Thuja orientalis, respectively. Ricinus communis were represented about 90% higher activity, two samples(Rosa rugosa and Sophorae Flos) showed 80% higher activity than the control. Three samples of plant extracts (Zanthoxylum piperitum, Pueraria thunbergiana, Solanum nigrum) were about 70% higher activity compared with the non-treated control. Cytotoxicity of plant extracts was not detected in the rat neural stem cells. These results suggest that the selected eight plant extracts are safe compounds. Our findings indicate that Wnt/β-catenin pathway reporter activity could be used for high throughput screening system. In addition, the plant extracts selected as candidates for adipocyte differentiation inhibiting may be potential therapeutic agents for obesity, it will be exploring the possibility of developing an anti-obesity materials through further experiments with selected plant extracts.