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  • Title: Network analysis and mechanisms of action of Chinese herb-related natural compounds in lung cancer cells.
    Author: Lin YJ, Liang WM, Chen CJ, Tsang H, Chiou JS, Liu X, Cheng CF, Lin TH, Liao CC, Huang SM, Chen J, Tsai FJ, Li TM.
    Journal: Phytomedicine; 2019 May; 58():152893. PubMed ID: 30901663.
    Abstract:
    BACKGROUND: Chinese herbal medicines (CHMs) are a resource of natural compounds (ingredients) and their potential chemical derivatives with anticancer properties, some of which are already in clinical use. Bei-Mu (BM), Jie-Geng (JG), and Mai-Men-Dong-Tang (MMDT) are important CHMs prescribed for patients with lung cancer that have improved the survival rate. HYPOTHESIS/PURPOSE: The aim of this study was to systemically investigate the mechanisms of action of these CHM products in lung cancer cells. METHODS: We used a network pharmacology approach to study CHM product-related natural compounds and their lung cancer targets. In addition, the underlying anti-lung cancer effects of the natural compounds on apoptosis, cell cycle progression, autophagy, and the expression of related proteins was investigated in vitro. RESULTS: Ingredient-lung cancer target network analysis identified 20 natural compounds. Three of these compounds, ursolic acid, 2-(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano(6,5-f)chromen-3-yl)-5-methoxyphenol, and licochalcone A, inhibited the proliferation of A549 lung cancer cells in a dose-dependent manner. Signal pathway analyses suggested that these three ingredients may target cellular apoptosis, anti-apoptosis, and cell cycle-related proteins. These three ingredients induced apoptosis through the regulation of the expression of apoptotic and anti-apoptotic proteins, including B-cell lymphoma-2 and full-length and cleaved poly(ADP-ribose) polymerase proteins. They also induced cell cycle arrest in S and G2/M phases and autophagy in A549 cells. CONCLUSION: The pharmacological mechanisms of ingredients from MMDT on lung cancer may be strongly associated with their modulatory effects on apoptosis, autophagy, cell cycle progression, and cell proliferation.
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