Luteolin suppresses the metastasis of triple-negative breast cancer by reversing epithelial-to-mesenchymal transition via downregulation of β-catenin expression

Abstract

The metastasis of breast cancer is associated with dismal prognosis and high mortality due to the lack of effective treatment. Luteolin, a natural flavonoid compound, has been shown to exert antitumor activity in various types of cancers. However, the effects and mechanisms of luteolin on the metastasis of triple-negative breast cancer (TNBC) remain elusive. In the present study, we found that pretreatment of highly metastatic TNBC cell lines with luteolin dose‑dependently inhibited cell migration and invasion, and reversed epithelial-mesenchymal transition (EMT) as determined by altered morphological characteristics, downregulated epithelial markers and upregulated mesenchymal markers, and inhibited EMT-related transcription factors. In an in vivo metastasis experiment using a xenograft model, luteolin markedly inhibited lung metastases of breast cancer and the expression of EMT molecules vimentin and Slug in primary tumor tissues. Notably, luteolin also suppressed the expression of β-catenin mRNA and protein in vitro and in vivo. Furthermore, overexpression of β-catenin by adenoviruses blocked these benefits of luteolin on invasion and metastases of breast cancer. In conclusion, all these results indicated that luteolin effectively suppressed metastases of breast cancer by reversing EMT, which may be mediated by downregulation of β-catenin.