Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor
10.1016/j.jpha.2024.01.002
- Author:
Jia QI
1
;
Zhou YINYIN
;
Song LI
;
Shi XIMENG
;
Jiang XUAN
;
Tao RUIZHI
;
Wang AIYUN
;
Wu YUANYUAN
;
Wei ZHONGHONG
;
Zhang YINAN
;
Li XIAOMAN
;
Lu YIN
Author Information
1. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,China
- Keywords:
Baicalin;
Chronic stress;
Breast cancer metastasis;
β2-adrenergic receptor;
Epithelial-mesenchymal transition
- From:
Journal of Pharmaceutical Analysis
2024;14(7):1047-1062
- CountryChina
- Language:Chinese
-
Abstract:
Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria bai-calensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-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 bio-physical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-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 xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.
