α-Mangostin Induces Apoptosis and Suppresses Differentiation of 3T3-L1 Cells via Inhibiting Fatty Acid Synthase

Abstract

a-Mangostin, isolated from the hulls of Garcinia mangostana L., was found to have in vitro cytotoxicity against 3T3-L1 cells as well as inhibiting fatty acid synthase (FAS, EC 2.3.1.85). Our studies showed that the cytotoxicity of a-mangostin with IC 50 value of 20 mM was incomplicated in apoptotic events including increase of cell membrane permeability, nuclear chromatin condensation and mitochondrial membrane potential (DYm) loss. This cytotoxicity was accompanied by the reduction of FAS activity in cells and could be rescued by 50 mM or 100 mM exogenous palmitic acids, which suggested that the apoptosis of 3T3-L1 preadipocytes induced by a-mangostin was via inhibition of FAS. Futhermore, a-mangostin could suppress intracellular lipid accumulation in the differentiating adipocytes and stimulated lipolysis in mature adipocytes, which was also related to its inhibition of FAS. In addition, 3T3-L1 preadipocytes were more susceptible to the cytotoxic effect of a-mangostin than mature adipocytes. Further studies showed that a-mangostin inhibited FAS probably by stronger action on the ketoacyl synthase domain and weaker action on the acetyl/malonyl transferase domain. These findings suggested that a-mangostin might be useful for preventing or treating obesity.