Baicalein inhibits NSCLC invasion and metastasis by reducing ezrin tension in inflammation microenvironment.

Baicalein, a flavonoid phytochemical, has been proved to be effective in anti-metastatic activity for various cancers, especially for non-small cell lung cancer (NSCLC). However, the underlying mechanism of how Baicalein targets the cellular mechanical activities during NSCLC cell invasion and metastasis remains elusive. In this study, we found that non-cytotoxic concentration of Baicalein still retain anti-dissemination activity both in vitro and in vivo. Using the genetic encoding tension probe based on Forster resonance energy transfer (FRET) theory, Baicalein significantly decreases ezrin tension by down-regulating the cellular ezrin-SNO levels in NSCLC cells in the inflammatory microenvironment. Moreover, the decreased ezrin tension inhibits the formation of aggressive phenotype of NSCLC cells and leader cells in collective migration, and subsequently suppresses NSCLC dissemination. Baicalein restrains SNO-mediated ezrin tension via decreasing the expression level of iNOS. Overall this study demonstrates the novel mechanism of Baicalein in suppressing NSCLC invasion and metastasis from the perspective of mechanopharmacology and shows a new direction for drug development.