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

alpha-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 alpha-mangostin with IC50 value of 20 mu M was incomplicated in apoptotic events including increase of cell membrane permeability, nuclear chromatin condensation and mitochondrial membrane potential (Delta Psi m) 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 alpha-mangostin was via inhibition of FAS. Futhermore, alpha-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 alpha-mangostin than mature adipocytes. Further studies showed that alpha-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 alpha-mangostin might be useful for preventing or treating obesity.