Network analysis and mechanisms of action of Chinese herb-related natural compounds in lung cancer cells

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.