Bromodomain-containing protein 4 is critical for the antiproliferative and pro-apoptotic effects of gambogic acid in anaplastic thyroid cancer

Gambogic acid (GA) has been widely used as an anticancer drug for different tumors, including thyroid cancer. However, the potential function and molecular mechanisms of GA in anaplastic thyroid cancer (ATC) has not been illustrated thus far. The aim of the present study was to demonstrate the antitumor effects of GA on ATC cells and investigate its underlying molecular mechanisms. The results revealed that GA significantly decreased the viability and proliferation, as well as induced cell apoptosis in ATC cell lines. Next, it was demonstrated that GA decreased the expression of bromodomain-containing protein 4 (BRD4), which has been reported to function as an oncogene in various types of cancer. BRD4 expression was significantly higher in ATC tissues compared with that in adjacent normal thyroid tissues. In addition, BRD4 silencing significantly repressed the cell viability and proliferation, and increased the cell apoptotic rate in vitro, while it also delayed the tumor growth in vivo. Notably, ectopic BRD4 expression significantly weakened the biological effects of GA on ATC cells in vitro and in vivo, which suggested that GA served its anticancer functions partially via downregulating BRD4. In conclusion, BRD4, functioning as an oncogene in ATC, is important for the antiproliferative and pro-apoptotic effects of GA.