α-Mangostin suppresses proliferation and invasion in osteosarcoma cells via inhibiting fatty acid synthase

Abstract

• α-mangostin was able to induce human osteosarcoma cells apoptosis via downregulating fatty acid synthase (FASN) expression in dose-dependent manner. • α-mangostin, as a FASN inhibitor, plays a great role in regulated ER stress-related protein and signal protein expression. • α-mangostin induced FASN inhibition, which might influence osteosarcoma progression, invasion and migration. Fatty acid synthase (FASN) is highly expressed in multiple types of human cancers and is recognized as one of the therapeutic targets for treating cancer metastasis. α-Mangostin is a natural xanthone extracted from mangosteen fruit, and possesses various biological activities. In our previous studies, α-mangostin was found to inhibit FASN activity. The present study was designed to reveal the effects of α-mangostin on osteosarcoma and to reveal whether the mechanism of α-mangostin in anticancer activity is related to FASN inhibition. Cytotoxicity was assessed in osteosarcoma MG63, 143B and U2OS cells. Cell viability was detected by an MTT assay. The protein expression levels were detected by western blotting. Flow cytometry, Annexin V/propidium iodide dual staining and Hoechst 33258 staining were performed to assess the apoptotic effects. Wound healing and Transwell assays were used to detect the inhibitory effect of α-mangostin on osteosarcoma cells invasion and migration. We found that α-mangostin blocked FASN expression, inhibited osteosarcoma cell proliferation, invasion and migration in a dose-dependent manner. In addition, α-mangostin regulated endoplasmic reticulum transmembrane receptors and signal protein expression in osteosarcoma cells. These findings suggested that α-mangostin suppresses osteosarcoma cell proliferation and metastasis by inhibiting FASN expression, which provides a basis as a potential target for osteosarcoma treatment.