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Hepatocellular carcinoma is a common type of cancer that is usually associatedwith poor prognosis. In this study, we examined the in vitro and in vivo mechanismsof the traditional Vietnamese herb Zanthoxylum avicennae on the inhibition ofHA22T human hepatocellular carcinoma cell proliferation. HA22T cells were treatedwith different concentrations of Zanthoxylum avicennae extracts (YBBEs) and analyzedwith the MTT assay, western blot analysis, flow cytometry, siRNA transfectionassays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograftnude mouse model was applied to confirm the cellular effects. YBBEs showed a stronginhibition of HA22T cell viability in a dose-dependent manner and significantlyreduced cell proliferation-related proteins as well as induced cell cycle arrestin the G2/M phase. Protein phosphatase 2A (PP2A) siRNA or okadaic acid totallyblocked YBBE-mediated cell proliferation inhibition. In addition, an HA22T-implantednude mouse model further confirmed that YBBEs inhibit HA22T tumor cell growthand downregulate the survival and cell cycle regulating proteins, as well as activatethe PP2A protein. Our findings indicate that the inhibition of HA22T cell proliferationby YBBEs is mediated through PP2A activation.

international journal of molecular medicine

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