Zanthoxylum avicennae extracts inhibit cell proliferation through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells in vitro and in vivo

Abstract

Hepatocellular carcinoma is a common type of cancer that is usually associated with poor prognosis. In this study, we examined the in vitro and in vivo mechanisms of the traditional Vietnamese herb Zanthoxylum avicennae on the inhibition of HA22T human hepatocellular carcinoma cell proliferation. HA22T cells were treated with different concentrations of Zanthoxylum avicennae extracts (YBBEs) and analyzed with the MTT assay, western blot analysis, flow cytometry, siRNA transfection assays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograft nude mouse model was applied to confirm the cellular effects. YBBEs showed a strong inhibition of HA22T cell viability in a dose-dependent manner and significantly reduced cell proliferation-related proteins as well as induced cell cycle arrest in the G2/M phase. Protein phosphatase 2A (PP2A) siRNA or okadaic acid totally blocked YBBE-mediated cell proliferation inhibition. In addition, an HA22T-implanted nude mouse model further confirmed that YBBEs inhibit HA22T tumor cell growth and downregulate the survival and cell cycle regulating proteins, as well as activate the PP2A protein. Our findings indicate that the inhibition of HA22T cell proliferation by YBBEs is mediated through PP2A activation.