Curcumin Modulates the Membrane Raft Integrity via Phase Separation and Induces CD44 Shedding in Tumor Cells

• DOI: 10.1021/acs.biochem.3c00645
• Publication Date: 2024-01-22T15:29:03Z
• Authors: Toshiyuki Murai; Yoshikazu Masaki; Kazuma Yasuhara
• Keywords: Lipid raft; ADAM10; Ectodomain; Cell membrane; Raft

CD44 is a transmembrane cell adhesion molecule that cleaved by the membrane proteinase, disintegrin and metalloproteinase 10 (ADAM10), on surface via ectodomain shedding after cholesterol depletion. Lipid raft-mediated essential for cancer invasion. As cell–cell cell–matrix adhesions are critical progression, lipid raft-targeting agents may be effective therapy. Here, we found curcumin its derivatives induced ADAM10-mediated of in tumor cells. We also membrane-active compounds whose effect depends planar backbone spatial arrangement methoxy groups substituted two aromatic rings using giant unilamellar plasma vesicles. Curcumin with rigid backbones hydroxy exerted membrane-domain-modulating activity, which account their pleiotropic effects multiple signaling pathways involving receptors. This study provides basis use compounds, such as curcuminoids, to elucidate roles rafts cellular signaling, regulation membrane-bound ADAM metalloproteinases, development novel lipid-based therapies.