Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptorOA
Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting β2-adrenergic receptor
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.
Qi Jia;Yinan Zhang;Xiaoman Li;Yin Lu;Yinyin Zhou;Li Song;Ximeng Shi;Xuan Jiang;Ruizhi Tao;Aiyun Wang;Yuanyuan Wu;Zhonghong Wei
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,ChinaJiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,China||Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine,Nanjing University of Chinese Medicine,Nanjing,210023,China||Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine(TCM)Prevention and Treatment of Tumor,Nanjing University of Chinese Medicine,Nanjing,210023,ChinaJiangsu Key Laboratory for Functional Substances of Chinese Medicine,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,China||Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,210023,China
BaicalinChronic stressBreast cancer metastasisβ2-adrenergic receptorEpithelial-mesenchymal transition
《药物分析学报（英文）》 2024 (007)
1047-1062 / 16
This work was supported by the Matching Grant of National Natural Science Foundation of China from Nanjing University of Chinese Medicine(Grant Nos.:NZY81903857,and NZY81703765),the National Natural Science Foundation of China(Grant No.:21877062),the Opening Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine(Grant No.:2020YLXK020),and Postgraduate Research & Practice Inno-vation Program of Jiangsu Province(Grant Nos.:SJCX21_0707,KYCX21_1772,and KYCX22_2039).We thank the Experiment Center for Science and Technology,Nanjing University of Chinese Medicine for valuable help in the experiment.
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