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BackgroundFatty acid synthase (FAS) has been proven over-expressed in human breast cancer cells and consequently, has been recognized as a target for breast cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen pericarp, has a variety of biological activities, including anti-cancer effect. In our previous study, alpha-mangostin had been found both fast-binding and slow-binding inhibitions to FAS in vitro. This study was designed to investigate the activity of alpha-mangostin on intracellular FAS activity in FAS over-expressed human breast cancer cells, and to testify whether the anti-cancer activity of alpha-mangostin may be related to its inhibitory effect on FAS.MethodsWe evaluated the cytotoxicity of alpha-mangostin in human breast cancer MCF-7 and MDA-MB-231 cells. Intracellular FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Cell Counting Kit assay was used to test the cell viability. Immunoblot analysis was performed to detect FAS expression level, intracellular fatty acid accumulation and cell signaling (FAK, ERK1/2 and AKT). Apoptotic effects were detected by flow cytometry and immunoblot analysis of PARP, Bax and Bcl-2. Small interfering RNA was used to down-regulate FAS expression and/or activity.ResultsAlpha-mangostin could effectively suppress FAS expression and inhibit intracellular FAS activity, and result in decrease of intracellular fatty acid accumulation. It could also reduce cell viability, induce apoptosis in human breast cancer cells, increase in the levels of the PARP cleavage product, and attenuate the balance between anti-apoptotic and pro-apoptotic proteins of the Bcl-2 family. Moreover, alpha-mangostin inhibited the phosphorylation of FAK. However, the active forms of AKT, and ERK1/2 proteins were not involved in the changes of FAS expression induced by alpha-mangostin.ConclusionsAlpha-mangostin induced breast cancer cell apoptosis by inhibiting FAS, which provide a basis for the development of xanthone as an agent for breast cancer therapy.

An atom‐precise Cu0‐containing copper cluster, Cu14(C2B10H10S2)6(CH3CN)8 (abbreviated as Cu14‐8CH3CN) is reported, which is synthesized via a simultaneous reduction strategy and fully characterized by single‐crystal X‐ray diffraction, ESI‐TOF‐MS, and X‐ray photoelectron spectroscopy. Cu14‐8CH3CN is the only copper cluster that has a virtually identical silver structural analog, i.e., Ag14(C2B10H10S2)6(CH3CN)8 (hereafter as Ag14‐8CH3CN). Nevertheless, density functional theory calculations reveal that the electronic structure of Cu14‐8CH3CN differs significantly from the superatom electronic configuration of Ag14‐8CH3CN. Moreover, Cu14‐8CH3CN shows room‐temperature luminescence and good electrocatalytic activities in the ethanol oxidation reaction and detection of H2O2. This pair of unprecedented analogous molecular nanoscale systems offer an ideal platform to investigate the fundamental differences between copper and silver in terms of catalytic activity and optical properties.

α-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 α-mangostin with IC50 value of 20 µM was incomplicated in apoptotic events including increase of cell membrane permeability, nuclear chromatin condensation and mitochondrial membrane potential (ΔΨm) loss. This cytotoxicity was accompanied by the reduction of FAS activity in cells and could be rescued by 50 µM or 100 µM exogenous palmitic acids, which suggested that the apoptosis of 3T3-L1 preadipocytes induced by α-mangostin was via inhibition of FAS. Futhermore, α-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 α-mangostin than mature adipocytes. Further studies showed that α-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 α-mangostin might be useful for preventing or treating obesity.

Fatty acid synthase (FAS) is highly expressed in many kinds of human cancers, including liver cancer. Curcumin is the major active ingredient of Curcuma longa and has long been used to treat a variety of maladies. In the present study, we investigated the potential use of curcumin as a kind of FAS inhibitor for chemoprevention of liver cancer. Curcumin induced HepG2 cell apoptosis with the IC50 value of 8.84 μg/ml. It inhibited intracellular FAS activity, and downregulated expression and mRNA level of FAS in a dose-dependent manner. In addition, sodium palmitate could rescue cell apoptosis induced by curcumin. Further studies reviewed that siRNA of FAS showed similar results as curcumin. These findings suggested that curcumin might be useful for preventing or treating liver cancer.