• Title/Summary/Keyword: Wnt pathway

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Pathways Analysis of Gleditsia spina Extract on Changes of Gene Expression in Human Melanoma cells (조각자(皂角刺)가 악성흑색종 세포주에 미치는 영향)

  • Kim, Bu-Yeo;Lim, Se-Hyun;Lee, Byoung-Ho;Lim, Chi-Yeon;Kim, Yong-Seong;Cho, Su-In
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.3
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    • pp.47-62
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    • 2009
  • Glenditsia spina (GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. For these reasons, GS has been widely used as dermatologic agent clinically. In this study, the specific pathways of anti-proliferative effect of GS on human derived melanoma cells were identified. The molecular profile was measured using microarray technique to identify up- or down-regulated genes in SK-MEL-2 cell line. Pathway analysis was done by listing percentage of pathway involvement, and the represented pathways were obtained from KEGG. The transcription factor binding sequences were obtained by Transfac database. By the promoter analysis, up-regulated genes by GS were mainly associated with MAPK, Regulation of actin cytoskeleton, Wnt, Focal adhesion and Long term potentiation pathway. Down-regulated genes by GS were mainly associated with MAPK and Antigen processing and presentation pathway. And some of the transcription factors like Sp1 and NF-Y in up-regulated genes and Oct-1 in down-regulated genes by GS also identified.

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Effect of Saussurea Lappa Root Extract on Proliferation and Hair Growth-related Signal Pathway in Human Hair Follicle Dermal Papilla Cells (당목향 뿌리 추출물의 인체 모유두세포 증식 및 모발 성장 관련 신호전달에 미치는 영향)

  • Chio, Hyoung-Chul;Jeong, Noh-Hee
    • Applied Chemistry for Engineering
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    • v.32 no.6
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    • pp.647-652
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    • 2021
  • In this study, Saussurea Lappa roots were extracted using ethanol and n-hexane, and also the effects on proliferation of human hair dermal papilla cells and fibroblast and related signaling pathway were evaluated. 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay was conducted for cell proliferation effect of Saussurea Lappa root extract, and extracellular signal-related kinase (ERK), serine/threonine protein kinase (Akt), wingless-related integration site (Wnt)/𝛽-catenin signaling pathway, and 5𝛼-reductase expression through western blot analysis were measured. Saussurea Lappa root extract significantly increased human hair dermal papilla cells and propagation of fibroblast, promoted phosphorylation of ERK and Akt that get involved in cell proliferation. Additionally, Saussurea Lappa root extract significantly decreased promotion of Akt phosphorylation and cell proliferation by MEK/ERK inhibitor PD98059 and PI3K/Akt inhibitor LY294002. Also, Saussurea Lappa root extract induced intranuclear 𝛽-catenin accumulation by promoting phosphorylation of 𝛽-catenin (Ser552, 675) through phosphorylation of GSK-3𝛽 (Ser9), and suppressed activation of 5𝛼-reductase type I and II. Overall, Saussurea Lappa root induces cell proliferation through vitalization of ERK and Akt route of human hair dermal papilla cells and fibroblast and apoptosis defense mechanism, and can be helpful in hair loss prevention and hair growth by vitalizing the 𝛽-catenin signaling pathway and inhibiting activation of 5𝛼-reductase, which can be used as a potential hair care products.

STAT3 Potentiates SIAH-1 Mediated Proteasomal Degradation of β-Catenin in Human Embryonic Kidney Cells

  • Shin, Minkyung;Yi, Eun Hee;Kim, Byung-Hak;Shin, Jae-Cheon;Park, Jung Youl;Cho, Chung-Hyun;Park, Jong-Wan;Choi, Kang-Yell;Ye, Sang-Kyu
    • Molecules and Cells
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    • v.39 no.11
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    • pp.821-826
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    • 2016
  • The ${\beta}$-catenin functions as an adhesion molecule and a component of the Wnt signaling pathway. In the absence of the Wnt ligand, ${\beta}$-catenin is constantly phosphorylated, which designates it for degradation by the APC complex. This process is one of the key regulatory mechanisms of ${\beta}$-catenin. The level of ${\beta}$-catenin is also controlled by the E3 ubiquitin protein ligase SIAH-1 via a phosphorylation-independent degradation pathway. Similar to ${\beta}$-catenin, STAT3 is responsible for various cellular processes, such as survival, proliferation, and differentiation. However, little is known about how these molecules work together to regulate diverse cellular processes. In this study, we investigated the regulatory relationship between STAT3 and ${\beta}$-catenin in HEK293T cells. To our knowledge, this is the first study to report that ${\beta}$-catenin-TCF-4 transcriptional activity was suppressed by phosphorylated STAT3; furthermore, STAT3 inactivation abolished this effect and elevated activated ${\beta}$-catenin levels. STAT3 also showed a strong interaction with SIAH-1, a regulator of active ${\beta}$-catenin via degradation, which stabilized SIAH-1 and increased its interaction with ${\beta}$-catenin. These results suggest that activated STAT3 regulates active ${\beta}$-catenin protein levels via stabilization of SIAH-1 and the subsequent ubiquitin-dependent proteasomal degradation of ${\beta}$-catenin in HEK293T cells.

Methylation of SFRPs and APC Genes in Ovarian Cancer Infected with High Risk Human Papillomavirus

  • Al-Shabanah, Othman Abdulla;Hafez, Mohamed Mahmoud;Hassan, Zeinab Korany;Sayed-Ahmed, Mohamed Mohamed;Abozeed, Waleed Nabeel;Alsheikh, Abdulmalik;Al-Rejaie, Salem Saleh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2719-2725
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    • 2014
  • Background: Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. Materials and Methods: DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. Results: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. Conclusion: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.

Immunohistochemical Analysis of TBX3 and $\beta$-catenin in Gastric Cancers

  • Song, Jae-Hwi;Yoon, Jung-Hwan;Kang, Young-Hwi;Cao, Zhang;Nam, Suk-Woo;Lee, Jung-Young;Park, Won-Sang
    • Molecular & Cellular Toxicology
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    • v.5 no.4
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    • pp.328-334
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    • 2009
  • TBX3 has demonstrated oncogenic activity as a downstream target of the Wnt/$\beta$-catenin signaling pathway. In this study, the aim was to determine whether overexpression of the TBX3 protein is involved in the development and/or progression of gastric cancers. We analyzed the expression pattern of the TBX3 and $\beta$-catenin proteins in a series of 186 sporadic gastric cancers. Altered expression of the TBX3 and $\beta$-catenin proteins was observed in 54 (29.0%) and 48 (25.8%) of the 186 gastric cancers. Statistically, overexpression of the TBX3 and $\beta$-catenin proteins was not associated with the clinical and pathological parameters studied including: histological type, tumor location, tumor size, and the 5-year survival (P>0.05). However, TBX3 overexpression was closely associated with lymph node metastasis and aberrant $\beta$-catenin expression (P<0.05). In addition, overexpression of the TBX3 protein was confirmed by Western blot analysis of primary gastric cancer tissues and cell lines. These data suggest that TBX3 overexpression may play a role in the development and progression of sporadic gastric cancers.

Regulatory Effect of Cannabidiol (CBD) on Decreased β-Catenin Expression in Alopecia Models by Testosterone and PMA Treatment in Dermal Papilla Cells

  • Park, Yoon-Jong;Ryu, Jae-Min;Na, Han-Heom;Jung, Hyun-Suk;Kim, Bokhye;Park, Jin-Sung;Ahn, Byung-Soo;Kim, Keun-Cheol
    • Journal of Pharmacopuncture
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    • v.24 no.2
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    • pp.68-75
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    • 2021
  • Objectives: The hair follicle is composed of more than 20 kinds of cells, and mesoderm derived dermal papilla cells and keratinocytes cooperatively contribute hair growth via Wnt/β-catenin signaling pathway. We are to investigate β-catenin expression and regulatory mechanism by CBD in alopecia hair tissues and dermal papilla cells. Methods: We performed structural and anatomical analyses on alopecia patients derived hair tissues using microscopes. Pharmacological effect of CBD was evaluated by β-catenin expression using RT-PCR and immunostaining experiment. Results: Morphological deformation and loss of cell numbers in hair shaft were observed in alopecia hair tissues. IHC experiment showed that loss of β-catenin expression was shown in inner shaft of the alopecia hair tissues, indicating that β-catenin expression is a key regulatory function during alopecia progression. Consistently, β-catenin expression was decreased in testosterone or PMA treated dermal papilla cells, suggesting that those treatments are referred as a model on molecular mechanism of alopecia using dermal papilla cells. RT-PCR and immunostaining experiments showed that β-catenin expression was decreased in RNA level, as well as decreased β-catenin protein might be resulted from ubiquitination. However, CBD treatment has no changes in gene expression including β-catenin, but the decreased β-catenin expression by testosterone or PMA was restored by CBD pretreatment, suggesting that potential regulatory effect on alopecia induction of testosterone and PMA. Conclusion: CBD might have a modulating function on alopecia caused by hormonal or excess of signaling pathway, and be a promising application for on alopecia treatment.

Differential effects of type 1 diabetes mellitus and subsequent osteoblastic β-catenin activation on trabecular and cortical bone in a mouse mode

  • Chen, Sixu;Liu, Daocheng;He, Sihao;Yang, Lei;Bao, Quanwei;Qin, Hao;Liu, Huayu;Zhao, Yufeng;Zong, Zhaowen
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.3.1-3.14
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    • 2018
  • Type 1 diabetes mellitus (T1DM) is a pathological condition associated with osteopenia. $WNT/{\beta}$-catenin signaling is implicated in this process. Trabecular and cortical bone respond differently to $WNT/{\beta}$-catenin signaling in healthy mice. We investigated whether this signaling has different effects on trabecular and cortical bone in T1DM. We first established a streptozotocin-induced T1DM mouse model and then constitutively activated ${\beta}$-catenin in osteoblasts in the setting of T1DM (T1-CA). The extent of bone loss was greater in trabecular bone than that in cortical bone in T1DM mice, and this difference was consistent with the reduction in the expression of ${\beta}$-catenin signaling in the two bone compartments. Further experiments demonstrated that in T1DM mice, trabecular bone showed lower levels of insulin-like growth factor-1 receptor (IGF-1R) than the levels in cortical bone, leading to lower $WNT/{\beta}$-catenin signaling activity through the inhibition of the IGF-1R/Akt/glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) pathway. After ${\beta}$-catenin was activated in T1-CA mice, the bone mass and bone strength increased to substantially greater extents in trabecular bone than those in cortical bone. In addition, the cortical bone of the T1-CA mice displayed an unexpected increase in bone porosity, with increased bone resorption. The downregulated expression of WNT16 might be responsible for these cortical bone changes. In conclusion, we found that although the activation of $WNT/{\beta}$-catenin signaling increased the trabecular bone mass and bone strength in T1DM mice, it also increased the cortical bone porosity, impairing the bone strength. These findings should be considered in the future treatment of T1DM-related osteopenia.

Proliferative Activity of Polyporus umbellatus Extract from Mushrooms via the PI3K/Akt and Wnt/β-catenine signaling in HHDPCs (사람 모유두세포에서 PI3K/Akt와 Wnt/β-catenine 신호전달을 경유한 저령추출물의 세포증식 효과)

  • Lea-Minju Kang;Suk-Jong Kang;Yeun-Ja Mun
    • The Korea Journal of Herbology
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    • v.39 no.1
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    • pp.23-29
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    • 2024
  • Objectives : Polyporus umbellatus is a medicinal mushroom that has been used for over thousands years in Chinese medicine as a powerful diuretic to relieve fluid retention and edema. Dermal papilla is located at the bottom of the hair follicle and connected to the blood vessels where it gets the nutrients and oxygen to nurture hair follicle. This study examined the mechanism through which the ethanol extract of Polyporus umbellatus (EPU) promoted the proliferation of human dermal papilla cells (HHDPCs). Methods : To estimate the proliferative effects of EPU on HHDPCs, cell viability was estimated by thiazolyl blue tetrazolium bromide (MTT) assay. Western blotting was used to investgate the activation of ERK, phosphoinositide 3-kinase (PI3K)/Akt, β-catenin, GSK-3β and heme oxygenase-1 (HO-1). Cells were treated with inhibitors of ERK and Akt prior to EPU treatment. Results : EPU promoted the proliferation of HHDPCs and the phosphorylation of ERK and Akt in dose dependent manner. However, the proliferative effect of EPU on HHDPCs was inhibited by pre-treatment of ERK inhibitor (PD98059) and Akt inhibitor (LY294002). Furthermore, EPU respectively stimulated the protein expression of β-catenin and phosphorylated GSK-3β. EPU significantly increased the protein expression levels of proliferation and cytoprotection related genes such as Bcl-2, SIRT-1, and HO-1 in cells. Conclusion : This results suggest that EPU promoted the proliferation of HHDPCs via activating PI3K/Akt and Wnt/β-catenin signaling pathway in HHDPCs.