Department of Pathology, College of Korean Medicine, Dong-eui University, Busan 47227, Republic of Korea.
Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan 47227, Republic of Korea.
Molecules. 2023 Apr 12;28(8):3414. doi: 10.3390/molecules28083414.
Previous studies have indicated that the adrenergic receptor signaling pathway plays a fundamental role in chronic stress-induced cancer metastasis. In this study, we investigated whether an ethanol extract of leaves (EPF) traditionally used to treat stress-related symptoms by moving Qi could regulate the adrenergic agonist-induced metastatic ability of cancer cells. Our results show that adrenergic agonists including norepinephrine (NE), epinephrine (E), and isoproterenol (ISO) increased migration and invasion of MDA-MB-231 human breast cancer cells and Hep3B human hepatocellular carcinoma cells. However, such increases were completely abrogated by EPF treatment. E/NE induced downregulation of E-cadherin and upregulation of N-cadherin, Snail, and Slug. Such effects were clearly reversed by pretreatment with EPF, suggesting that the antimetastatic activity of EPF could be related to epithelial-mesenchymal transition (EMT) regulation. EPF suppressed E/NE-stimulated Src phosphorylation. Inhibition of Src kinase activity with dasatinib completely suppressed the E/NE-induced EMT process. Transfecting MDA-MB-231 cells with constitutively activated Src (SrcY527F) diminished the antimigration effect of EPF. Taken together, our results demonstrate that EPF can suppress the adrenergic agonist-promoted metastatic ability of cancer cells by inhibiting Src-mediated EMT. This study provides basic evidence supporting the probable use of EPF to prevent metastasis in cancer patients, especially those under chronic stress.
先前的研究表明，肾上腺素能受体信号通路在慢性应激诱导的癌症转移中起着至关重要的作用。在这项研究中，我们研究了传统上用于治疗与应激相关症状的 叶乙醇提取物 (EPF) 是否可以调节肾上腺素能激动剂诱导的癌细胞转移能力。我们的结果表明，包括去甲肾上腺素 (NE)、肾上腺素 (E) 和异丙肾上腺素 (ISO) 在内的肾上腺素能激动剂增加了 MDA-MB-231 人乳腺癌细胞和 Hep3B 人肝癌细胞的迁移和侵袭。然而，EPF 处理完全消除了这种增加。E/NE 诱导 E-钙粘蛋白下调和 N-钙粘蛋白、Snail 和 Slug 上调。EPF 的预处理明显逆转了这种作用，表明 EPF 的抗转移活性可能与上皮-间充质转化 (EMT) 调节有关。EPF 抑制 E/NE 刺激的Src 磷酸化。用达沙替尼抑制Src 激酶活性完全抑制了 E/NE 诱导的 EMT 过程。转染 MDA-MB-231 细胞中组成型激活的 Src (SrcY527F) 减弱了 EPF 的抗迁移作用。综上所述，我们的研究结果表明，EPF 可以通过抑制 Src 介导的 EMT 来抑制肾上腺素能激动剂促进的癌细胞转移能力。这项研究为 EPF 可能用于预防癌症患者，特别是慢性应激患者的转移提供了基础证据。
