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 IC.sub.50 value of 20 [micro]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 [micro]M or 100 [micro]M 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.