Euphol from Euphorbia tirucalli negatively modulates transforming growth factor‐beta (TGF‐β) responsiveness correlate with TGF‐β receptor segregation inside membrane rafts.

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/caveolae is membrane microdomain with important roles in cell survival signaling. Cholesterol is important for the structure and function of these microdomains. Our previous studies shown that cholesterol, alone or complexed in lipoproteins, suppresses TGF‐β responsiveness by lipid‐raft segregation of TGF‐β receptors and facilitating rapid degradation of TGF‐β and thus suppressing TGF‐β‐induced signaling. Euphol is an euphane‐type triterpene alcohol, is structurally similar to cholesterol and has a wide range of pharmacological properties including anti‐inflammation and anti‐cancer. In the present study, we demonstrated that euphol suppress TGF‐β signaling by moving TGF‐β receptor from non‐lipid raft to lipid‐raft microdomains in plasma membrane and increased degradation of TGF‐β receptors.