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

化学 乳腺癌 癌症研究 转移 乳腺癌转移 癌症 受体 黄芩苷 肾上腺素能的 慢性应激 药理学 癌症转移 内科学 医学 生物化学 高效液相色谱法 生物 色谱法
作者
Qi Jia,Yinyin Zhou,Li Song,Ximeng Shi,Xuan Jiang,Ruizhi Tao,Aiyun Wang,Yuanyuan Wu,Zhonghong Wei,Yinan Zhang,Xiaoman Li,Yin Lu
出处
期刊:Journal of Pharmaceutical Analysis [Elsevier BV]
卷期号:14 (7): 100934-100934 被引量:8
标识
DOI:10.1016/j.jpha.2024.01.002
摘要

Recent studies have shown that stress can substantially facilitate breast cancer metastasis, which can be ameliorated 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 baicalensis 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 biophysical and biochemical assays. Furthermore, we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR, subsequently inhibit 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.
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