Chong Yuan1, Meng-Heng Wang1, Fei Wang1, Peng-Yu Chen1, Xin-Ge Ke1, Bing Yu1, Yan-Fang Yang2, Peng-Tao You3, He-Zhen Wu4. 1. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China. 2. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan 430061, China. Electronic address: yyf0204@hbtcm.edu.cn. 3. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan 430061, China. Electronic address: tptyou@hbtcm.edu.cn. 4. Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan 430061, China. Electronic address: 1446@hbtcm.edu.cn.
Abstract
AIMS: Scopoletin is a natural anticarcinogenic and antiviral coumarin component. Many studies have proved its anti-cancer effect, and after the preliminary screening of this study, Scopoletin had the best inhibitory effect on Non-small cell lung cancer (NSCLC). But its mechanism for treating NSCLC is still unclear. Therefore, network pharmacology and molecular docking technology were used to explore the potential anti-NSCLC targets and pathways of Scopoletin. The results were verified in vitro. MAIN METHODS: First, Scopoletin was isolated from Fennel and screened to conduct cell proliferation assay on Human lung cancer cell line A549, Human colon cancer cell line HCT-116 and Human hepatoma cell line HepG2 respectively, through the MTT test. Then, the key targets and related pathways were screened through Protein-protein Interaction (PPI) network and "component-target-pathway" (C-TP) network constructed by network pharmacology. And the key targets were selected to dock with Scopoletin via molecular docking. A549 and Human normal lung epithelial cell BEAS-2B were used to verify the results, finally. KEY FINDINGS: Through MTT, A549 was chosen as the test cancer cell. From network pharmacology, 16 targets, 27 signaling pathways and 16 GO items were obtained (P < 0.05). The results of PPI network and molecular docking showed that EGFR, BRAF and AKT1 were the key targets of Scopoletin against NSCLC, which were consistent with the western-blot results. SIGNIFICANCE: Through network pharmacology, molecular docking and experiments in vitro, Scopoletin was verified to against NSCLC through RAS-RAF-MEK-ERK pathway and PI3K/AKT pathway.
AIMS: Scopoletin is a natural anticarcinogenic and antiviral coumarin component. Many studies have proved its anti-cancer effect, and after the preliminary screening of this study, Scopoletin had the best inhibitory effect on Non-small cell lung cancer (NSCLC). But its mechanism for treating NSCLC is still unclear. Therefore, network pharmacology and molecular docking technology were used to explore the potential anti-NSCLC targets and pathways of Scopoletin. The results were verified in vitro. MAIN METHODS: First, Scopoletin was isolated from Fennel and screened to conduct cell proliferation assay on Humanlung cancer cell line A549, Humancolon cancer cell line HCT-116 and Humanhepatoma cell line HepG2 respectively, through the MTT test. Then, the key targets and related pathways were screened through Protein-protein Interaction (PPI) network and "component-target-pathway" (C-TP) network constructed by network pharmacology. And the key targets were selected to dock with Scopoletin via molecular docking. A549 and Human normal lung epithelial cell BEAS-2B were used to verify the results, finally. KEY FINDINGS: Through MTT, A549 was chosen as the test cancer cell. From network pharmacology, 16 targets, 27 signaling pathways and 16 GO items were obtained (P < 0.05). The results of PPI network and molecular docking showed that EGFR, BRAF and AKT1 were the key targets of Scopoletin against NSCLC, which were consistent with the western-blot results. SIGNIFICANCE: Through network pharmacology, molecular docking and experiments in vitro, Scopoletin was verified to against NSCLC through RAS-RAF-MEK-ERK pathway and PI3K/AKT pathway.
Authors: Fatima Noor; Muhammad Tahir Ul Qamar; Usman Ali Ashfaq; Aqel Albutti; Ameen S S Alwashmi; Mohammad Abdullah Aljasir Journal: Pharmaceuticals (Basel) Date: 2022-05-04