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

中草药相关天然化合物在肺癌细胞中的网络分析及作用机制

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作者:Ying-Ju Lin, Wen-Miin Liang, Chao-Jung Chen, Hsinyi Tsang, Jian-Shiun Chiou, Xiang Liu, Chi-Fung Cheng, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Jianxin Chen, Fuu-Jen Tsai, Te-Mao Li

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/

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.

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.

Purpose

The aim of this study was to systemically investigate the mechanisms of action of these CHM products in lung cancer cells.

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.

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