Ethoxysanguinarine inhibits viability and induces apoptosis of colorectal cancer cells by inhibiting CIP2A

Cancerous inhibitor of protein phosphatase 2A (CIP2A) an endogenous inhibitor of protein phosphatase 2A (PP2A), which can promote proliferation and transformation of several cancer types, has been shown to be a target for tumor therapy. The present study investigated the effects and underlying mechanisms of action of a novel natural compound, ethoxysanguinarine (Eth), on colorectal cancer (CRC) cells. MTT assay and flow cytometric assay found that Eth inhibited the viability and induced the apoptosis of the CRC cells. The inhibition of viability and activation of apoptosis was mediated through the Eth-induced decrease in CIP2A expression. Knockdown of CIP2A by RNA interference sensitized, whereas overexpression of CIP2A antagonized, Eth-induced viability inhibition and apoptosis. Furthermore, western blot analysis suggested that Eth inhibited phosphorylation of CIP2A downstream molecule protein kinase B via the activation of PP2A. CRC xenograft tests also confirmed the antitumor effect of Eth in vivo. These results advance our understanding of Eth-induced viability inhibition and apoptosis, implying the requirement for further investigation of Eth as a CIP2A inhibitor for cancer therapies.