Abstract B52: Brusatol inhibits oral squamous cell carcinoma cells by targeting glycolytic metabolism

Brusatol is a natural terpenoid that is isolated from the Brucea javanica plant, a medicine plant distributed widely throughout Asia, and its bitter fruits have been used traditionally in medicine for treating various ailments and controlling some pests. Brusatol has recently been shown to be capable of inducing a variety of biologic effects, including a potential antitumor effect. The goal of this study was to investigate the role of brusatol in oral squamous cell carcinoma (OSCC) cells and its mechanism. Brusatol treatment had broad effects against oral cancer cells in vitro including inhibition of proliferation, colony formation, cell migration and invasion, and induction of apoptosis. Mechanism studies showed that brusatol inhibited glucose uptake and lactate secretion and glycolytic pathway key enzymes HK and PK activity in vitro. Brusatol inhibited glycolysis, glycolytic capacity, and reserve capacity by Seahorse XF glycolysis stress test assay. In vivo study showed that brusatol suppresses tumor growth in a nude mouse xenograft model by inhibiting cell proliferation and angiogenesis and by inducing apoptosis. Glycolysis-related genes were also deceased in the nude mice xenografts. Taken together, these data clearly indicated that brusatol is a promising chemotherapeutic agent for OSCC treatment. Citation Format: Guilian Zhang, Ying Su, Suhong Chen, Xinyan Zhang. Brusatol inhibits oral squamous cell carcinoma cells by targeting glycolytic metabolism [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B52.