Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor. - GreenMedInfo Summary

Recent studies have shown that stress can substantially facilitate breast cancer metastasis, which can be reduced by nonselectiveβ1/β2-adrenergic receptor (β1/β2-AR) blocker. However, several side effects were identified. Thus, it is extremely warranted to explore more effective and better-toleratedβ2-AR blocker. Currently, we demonstrated that baicalin (BA), a major bioactive component ofGeorgi, could significantly attenuate stress hormones especially epinephrine (Epi)-induced breast cancer cell migration and invasionMechanistically, we identified thatβ2-AR was a direct target of BA via the drug affinity responsive target stability (DARTS) combined with mass spectrum assay, and BA photoaffinity probe with pull-down assay, which was further confirmed by a couple of biophysical and biochemical assays. Furthermore, we demonstrated that BA could directly bind to the Phe-193 and Phe-289 ofβ2-AR, subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase (cAMP-PKA-FAK) pathway, and thus impede epithelial-mesenchymal transition (EMT), thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograftorthotopic and tail vein mouse model. These findings firstly identify BA as a potentialβ2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.