Alpha-mangostin dephosphorylates ERM to induce adhesion and decrease surface stiffness in KG-1 cells.

Surface stiffness is a unique indicator of various cellular states and events and needs to be tightly controlled. α-Mangostin, a natural compound with numerous bioactivities, reduces the mechanical stiffness of various cells; however, the mechanism by which it affects the actin cytoskeleton remains unclear. We aimed to elucidate the mechanism underlying α-mangostin activity on the surface stiffness of leukocytes. We treated spherical non-adherent myelomonocytic KG-1 cells with α-mangostin; it clearly reduced their surface stiffness and disrupted their microvilli. The α-mangostin-induced reduction in surface stiffness was inhibited by calyculin A, a protein phosphatase inhibitor. α-Mangostin also induced KG-1 cell adhesion to a fibronectin-coated surface. In KG-1 cells, a decrease in surface stiffness and the induction of cell adhesion are largely attributed to the dephosphorylation of ezrin/radixin/moesin proteins (ERMs); α-mangostin reduced the levels of phosphorylated ERMs. It further increased protein kinase C (PKC) activity. α-Mangostin-induced KG-1 cell adhesion and cell surface softness were inhibited by the PKC inhibitor GF109203X. The results of the present study suggest that α-mangostin decreases stiffness and induces adhesion of KG-1 cells via PKC activation and ERM dephosphorylation. [ABSTRACT FROM AUTHOR]