Inhibitory effects of garcinone E on fatty acid synthase.

Fatty acid synthase (FAS) is highly expressed in human adipocytes and cancer cells and is considered as a dual therapeutic target for obesity and cancer treatment. Garcinone E is a natural xanthone and exists in the pericarp of . In previous studies, xanthones were reported to be highly active inhibitors of FAS. In the present study, the detailed inhibitory mechanism of garcinone E on FAS was investigated. We found that garcinone E inhibited the activity of FAS in a concentration-dependent manner with a half-inhibitory concentration value of 3.3 μM. The inhibition kinetic results showed that the inhibition of FAS by garcinone E was competitive with respect to acetyl-CoA, mixed competitive and noncompetitive with respect to malonyl-CoA, and noncompetitive to NADPH. In addition, garcinone E showed irreversible inhibition on FAS, which was different from all other xanthones. Since FAS is believed to be a therapeutic target for obesity and cancer treatment, these findings suggest the clinical potential of garcinone E in the prevention and treatment of both obesity and cancer.