Pterostilbene inhibits the metastasis of TNBC via suppression of β-catenin-mediated epithelial to mesenchymal transition and stemness

Abstract

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis and high mortality due to lack of effective treatment. The tendency of TNBC to metastasize to distinct organs is caused by cancer cells undergoing a particular mesenchymal phenotypic shift and enriched cancer stem cells (CSCs) in tumors. Pterostilbene (PTE), a bioactive phytoalexin naturally found in blueberries or grapes, has attracted considerable attention in terms of superior potential in cancer chemoprevention and chemotherapy applications. However, whether PTE can inhibit the metastasis of TNBC via regulating epithelial to mesenchymal transition (EMT) and stemness is still explored. In the present study, we found that PTE possessed the abilities of reversing EMT by upregulation of E-cadherin and downregulation of ZEB1 and SNAI1 and suppression of stemness by inhibiting the self-renewal capacity of mammosphere on tumor cells. Furthermore, PTE could inhibit the lung metastases of TNBC with therapeutic safety by suppressing the nuclear translocation of β-catenin to decrease the expression of target protein of CD44, MMPs. Our data demonstrated PTE possessed the effect against the metastasis of TNBC by suppression of β-catenin-mediated EMT and stemness, which may further enhance its dietary benefit and possibly contribute to a valuable clinical effect.