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

Chun-Lin Chen; Ying-Pin Chen; Ming-Wei Lin; Yaw-Bin Huang; Fang-Rong Chang; Tsai-Hui Duh; Deng-Chyang Wu; Wei-Chiang Wu; Yu-Chen Kao; Pei-Hua Yang

doi:10.1371/journal.pone.0140249

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

PLoS One. 2015 Oct 8;10(10):e0140249. doi: 10.1371/journal.pone.0140249. eCollection 2015.

Authors

Affiliations

¹ Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC; Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung, Taiwan, ROC; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
² Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC.
³ Department of Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
⁴ Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC; Department of Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
⁵ Graduate Institute of Nature Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
⁶ Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
⁷ Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
⁸ Faculty of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Euphorbia / chemistry
Fibronectins / genetics
Fibronectins / metabolism
Gene Expression
Humans
Lanosterol / analogs & derivatives*
Lanosterol / pharmacology
Membrane Microdomains / metabolism*
Phosphorylation
Plant Extracts / pharmacology*
Protein Processing, Post-Translational
Protein Transport
Proteolysis
Receptors, Transforming Growth Factor beta / metabolism*
Stomach Neoplasms
Transcriptional Activation
Transforming Growth Factor beta / physiology*

Substances

Fibronectins
Plant Extracts
Receptors, Transforming Growth Factor beta
Transforming Growth Factor beta
Lanosterol
euphol

Grants and funding

This work is supported by the National Science Council of Taiwan (101-2320-B-110-003, 102-2320-B-110-007, 103-2314-B-037-064, and 103-2320-B-037-014), KMU Center for Stem Cell Research (KMU-TP103G01, KMU-TP103G00, KMU-TP103G03, KMU-TP103G04 & KMU-TP103G05) and NSYSU-KMU Joint Research Project (NSYSUKMU2013-I006).