Diosmin induces cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and blocks tumour growth in xenografted nude mice

This study investigated the diosmin effect on HA22T human hepatocellular carcinoma cells in vitro and in an in vivo mouse xenograft model. HA22T cells were treated with different concentrations of diosmin and analysed with Western blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally, the HA22T-implanted xenograft nude mice model was applied to confirm the cellular effects. Diosmin induced apoptosis, up-regulated death receptor apoptotic pathway markers as well as mitochondrial proteins. Pro-survival Bcl-2 family proteins were inhibited and the pro-apoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or okadaic acid reversed the diosmin effects, confirming the role of PP2A in diosmin-induced HA22T apoptosis. The HA22T-implanted nude mice model revealed that diosmin inhibited tumour cell proliferation and enhanced tumour cell apoptosis. All our experimental evidence indicates that diosmin significantly promotes HA22T apoptosis and reduces tumour sizes in xenograft nude mice via PP2A in a dose-dependent manner.