Wnt signaling regulates various processes such as cell proliferation, differentiation, and embryo development. However, numerous diseases have been attributed to the aberrant transduction of Wnt signaling. We screened a plant extract library targeting TCF/β-catenin transcriptional modulating activity with a cell-based luciferase assay. Activity-guided fractionation of the MeOH extract of the E. longifolia root led to the isolation of 9-hydroxycanthin-6-one (1). Compound 1 exhibited TCF/β-catenin inhibitory activity. Compound 1 decreased the expression of Wnt signal target genes, mitf and zic2a, in zebrafish embryos. Treatment of SW480 cells with 1 decreased β-catenin and increased phosphorylated β-catenin (Ser 33, 37, Tyr 41) protein levels. The degradation of β-catenin by 1 was suppressed by GSK3β-siRNA, while compound 1 decreased β-catenin even in the presence of CK1α-siRNA. These results suggest that 1 inhibits Wnt signaling through the activation of GSK3β independent of CK1α.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jnatprod.5b00153 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cardiac Regeneration in Adult Zebrafish: A Review of Signaling and Metabolic Coordination.
Curr Cardiol Rep
January 2025
Department of Zoology, Trivenidevi Bhalotia College (Affiliated to Kazi Nazrul University), College Para Rd, Raniganj, 713347, West Bengal, India.
Purpose Of Review: This review investigates how post-injury cellular signaling and energy metabolism are two pivotal points in zebrafish's cardiomyocyte cell cycle re-entry and proliferation. It seeks to highlight the probable mechanism of action in proliferative cardiomyocytes compared to mammals and identify gaps in the current understanding of metabolic regulation of cardiac regeneration.
Recent Findings: Metabolic substrate changes after birth correlate with reduced cardiomyocyte proliferation in mammals.
Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway.
Cells
January 2025
Department of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
In neurons, the acquisition of a polarized morphology is achieved upon the outgrowth of a single axon from one of several neurites. Small extracellular vesicles (sEVs), such as exosomes, from diverse sources are known to promote neurite outgrowth and thus may have therapeutic potential. However, the effect of fibroblast-derived exosomes on axon elongation in neurons of the central nervous system under growth-permissive conditions remains unclear.
View Article and Find Full Text PDFKlotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.
Int J Mol Med
March 2025
Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis.
View Article and Find Full Text PDFEmerging Combinatorial Drug Delivery Strategies for Breast Cancer: A Comprehensive Review.
Curr Drug Targets
January 2025
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.) 470003, India.
Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action.
View Article and Find Full Text PDFSignaling Dynamics in Osteogenesis: Unraveling Therapeutic Targets for Bone Generation.
Curr Drug Targets
January 2025
Department of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL33458, United States.
Diseases affecting bone encompass a spectrum of disorders, from prevalent conditions such as osteoporosis and Paget's disease, collectively impacting millions, to rare genetic disorders including Fibrodysplasia Ossificans Progressiva (FOP). While several classes of drugs, such as bisphosphonates, synthetic hormones, and antibodies, are utilized in the treatment of bone diseases, their efficacy is often curtailed by issues of tolerability and high incidence of adverse effects. Developing therapeutic agents for bone diseases is hampered by the fact that numerous pathways regulating bone metabolism also perform pivotal functions in other organ systems.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!