Preliminary investigation on the mechanism of baicalein regulating the effects of Nischarin on invasion and apoptosis of human breast cancer cells MCF-7 through Wnt3α/β-catenin pathway

Abstract

BackgroundBreast cancer (BC) remains the leading cause of cancer-related mortality in women. Here, we investigate the anti-tumor effects of baicalein on human BC cells (MCF-7 cells) and explore if it regulates the Nischarin protein via Wnt3α/β-catenin signaling pathway. MethodsWe employed Wnt3α and DKK-1 to activate and inhibit the Wnt/β-catenin signaling pathway, respectively. We used CCK-8 cell viability, flow cytometry apoptosis, wound-healing and transwell migration/invasion assays. Further, using western blotting and real-time quantitative PCR (q-PCR) we analyzed expression levels of Nischarin, MMP-9, Wnt/β-catenin pathway (β-catenin, Axin 1), and apoptotic pathway (Bax, Bcl-2) proteins and their mRNAs. ResultsWe found that baicalein inhibits MCF-7 cell viability and promotes apoptosis (evidenced by increased Bax and decreased Bcl-2 expressions) in a concentration-dependent manner. It also inhibits TPA-induced migration and invasion, and downregulates MMP-9 expression. Baicalein reverses the increase in cell viability caused by Wnt3α-induced Wnt/β-catenin pathway activation. Conversely, baicalein counteracts the increase in apoptosis caused by DKK-1 mediated inhibition of the Wnt/β-catenin pathway. Additionally, baicalein upregulates Nischarin expression via modulating the Wnt/β-catenin pathway as indicated by the antagonistic effects of Wnt3α and DKK-1 on this effect of baicalein. ConclusionBaicalein exerts anti-tumor effects on MCF-7 cells through the Wnt3α/β-catenin signaling pathway, and promotes apoptosis and inhibits migration and invasion. The upregulation of Nischarin by baicalein further suggests a potential therapeutic target for BC treatment.