Euphol from Euphorbia tirucalli Negatively Modulates TGF-β Responsiveness via TGF-β Receptor Segregation inside Membrane Rafts

• Published in: PloS one Vol. 10; no. 10; p. e0140249
• Main Authors: Chen, Chun-Lin, Chen, Ying-Pin, Lin, Ming-Wei, Huang, Yaw-Bin, Chang, Fang-Rong, Duh, Tsai-Hui, Wu, Deng-Chyang, Wu, Wei-Chiang, Kao, Yu-Chen, Yang, Pei-Hua
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.10.2015; Public Library of Science (PLoS)
• Subjects: Alcohols; Anticancer properties; Antifungal agents; Apoptosis; Cancer; Caveolae; Cell Line, Tumor; Cell survival; Chemistry; Cholesterol; Clathrin; Endocytosis; Epidermal growth factor; Euphorbia - chemistry; Euphorbia tirucalli; Fibronectins - genetics; Fibronectins - metabolism; Gastric cancer; Gene Expression; Humans; Inflammation; Kinases; Lanosterol - analogs & derivatives; Lanosterol - pharmacology; Lipid rafts; Lipids; Medical research; Membrane Microdomains - metabolism; Natural products; Pharmaceutical sciences; Pharmacology; Pharmacy; Phosphorylation; Plant Extracts - pharmacology; Plasma; Protein Processing, Post-Translational; Protein Transport; Proteins; Proteolysis; Rafts; Receptors; Receptors, Transforming Growth Factor beta - metabolism; Signal transduction; Signaling; Stem cells; Stomach cancer; Stomach Neoplasms; Structure-function relationships; Transcriptional Activation; Transforming growth factor; Transforming Growth Factor beta - physiology; Transforming growth factor-b; Tumors; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0140249

Transforming growth factor-β (TGF-β) responsiveness in cultured cells can be modulated by TGF-β partitioning between lipid raft/caveolae- and clathrin-mediated endocytosis pathways. Lipid rafts are plasma membrane microdomains with an important role in cell survival signaling, and cholesterol is necessary for the lipid rafts' structure and function. Euphol is a euphane-type triterpene alcohol that is structurally similar to cholesterol and has a wide range of pharmacological properties, including anti-inflammatory and anti-cancer effects. In the present study, euphol suppressed TGF-β signaling by inducing TGF-β receptor movement into lipid-raft microdomains and degrading TGF-β receptors.