Inhibition of Adrenergic Agonist–Induced Metastatic Potential in Cancer Cells by an Ethanolic Extract of Lindera aggregata Root Tuber
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Objectives: The root tuber of Lindera aggregata (LA) has been traditionally used in Korean medicine to promote qi circulation and alleviate pain. This study investigated the antimetastatic effects of an ethanolic extract of LA (ELA) and explored its underlying molecular mechanisms. Methods: The effect of ELA on adrenergic agonist–induced cancer cell migration and invasion was evaluated using transwell assays. The influence of ELA on Src phosphorylation induced by adrenergic agonists was assessed via Western blot analysis. Network pharmacology analysis was conducted based on the known and predicted targets of ELA, including KEGG pathway enrichment, Gene Ontology (GO) enrichment, protein–protein interaction (PPI) network construction, and disease association analysis. Results: Migration of MDA-MB-231 breast cancer cells and Hep3B hepatocellular carcinoma cells was promoted by adrenergic agonists, including epinephrine (E), norepinephrine (NE), and isoprenaline (ISO). This effect was significantly reversed by ELA in a concentration- dependent manner. Similarly, E- and NE-induced cancer cell invasion was suppressed by ELA in a dose-dependent manner. ELA also inhibited E- and NE-stimulated Src phosphorylation, suggesting that the anti-metastatic effects of ELA are mediated through Src inactivation. Network pharmacology analysis identified Src as a central hub protein potentially mediating the effects of LA. In addition, enrichment analysis revealed significant involvement of LA targets in cancer-related pathways and cell motility processes, further supporting the experimental findings. Conclusion: These findings suggest that ELA inhibits adrenergic agonist–induced metastatic activity in cancer cells by deactivating Src, highlighting its potential as a novel antimetastatic therapeutic agent.
Abstract
Objectives: The root tuber of Lindera aggregata (LA) has been traditionally used in Korean medicine to promote qi circulation and alleviate pain. This study investigated the antimetastatic effects of an ethanolic extract of LA (ELA) and explored its underlying molecular mechanisms. Methods: The effect of ELA on adrenergic agonist–induced cancer cell migration and invasion was evaluated using transwell assays. The influence of ELA on Src phosphorylation induced by adrenergic agonists was assessed via Western blot analysis. Network pharmacology analysis was conducted based on the known and predicted targets of ELA, including KEGG pathway enrichment, Gene Ontology (GO) enrichment, protein–protein interaction (PPI) network construction, and disease association analysis. Results: Migration of MDA-MB-231 breast cancer cells and Hep3B hepatocellular carcinoma cells was promoted by adrenergic agonists, including epinephrine (E), norepinephrine (NE), and isoprenaline (ISO). This effect was significantly reversed by ELA in a concentration- dependent manner. Similarly, E- and NE-induced cancer cell invasion was suppressed by ELA in a dose-dependent manner. ELA also inhibited E- and NE-stimulated Src phosphorylation, suggesting that the anti-metastatic effects of ELA are mediated through Src inactivation. Network pharmacology analysis identified Src as a central hub protein potentially mediating the effects of LA. In addition, enrichment analysis revealed significant involvement of LA targets in cancer-related pathways and cell motility processes, further supporting the experimental findings. Conclusion: These findings suggest that ELA inhibits adrenergic agonist–induced metastatic activity in cancer cells by deactivating Src, highlighting its potential as a novel antimetastatic therapeutic agent.