Amentoflavone suppresses hepatocellular carcinoma by repressing hexokinase 2 expression through inhibiting JAK2/STAT3 signaling.

Hepatocellular carcinoma (HCC) has become a burden on public health worldwide. Therefore, development of novel therapeutic agents for managing HCC is imperative. Amentoflavone (AF), a flavonoid compound extracted from Selaginella tamariscina Spring, reportedly has anti-neoplastic activities. The aim of this study was to investigate the role of AF in HCC and the underlying mechanism of action. We found that AF decreased cell viability in a dose-dependent manner in both HCC cell lines but did not affect the viability of a normal hepatic cell line. The anti-growth effect of AF against HCC was also confirmed in the xenograft model. Standard histological examination of the xenograft tissues also revealed minimal in vivo toxicity of AF. The In vitro and in vivo models also provided evidence of the pro-apoptotic activity of AF. In addition, AF significantly inhibited glycolysis via HK2 repression; further dissection of the underlying mechanism revealed that AF downregulated HK2 by generating ROS and hence inhibiting the JAK2/STAT3 signaling pathway. In conclusion, AF induced apoptosis and inhibited glycolysis in HCC by targeting HK2. Our findings provide preliminary experimental data that support further investigation of the therapeutic efficacy of AF in HCC.