School of Chinese Medicine, China Medical University, Taichung, Taiwan; Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Graduate Institute of Biostatistics, School of Public Health, China Medical University, Taichung, Taiwan.
Phytomedicine. 2019 May;58:152893. doi: 10.1016/j.phymed.2019.152893. Epub 2019 Mar 13.
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.
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.
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.
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.
中草药（CHMs）是天然化合物（成分）及其潜在化学衍生物的资源，具有抗癌特性，其中一些已在临床应用。贝母、桔梗和麦冬汤是治疗肺癌患者的重要 CHM 方剂，已提高了生存率。
假设/目的：本研究旨在系统研究这些 CHM 产品在肺癌细胞中的作用机制。
我们使用网络药理学方法研究 CHM 产品相关的天然化合物及其肺癌靶点。此外，还在体外研究了天然化合物对细胞凋亡、细胞周期进展、自噬和相关蛋白表达的潜在抗癌作用。
成分-肺癌靶点网络分析确定了 20 种天然化合物。其中三种化合物，熊果酸、2-(3R)-8,8-二甲基-3,4-二氢-2H-吡喃(6,5-f)色烯-3-基)-5-甲氧基苯酚和甘草查尔酮 A，以剂量依赖性方式抑制 A549 肺癌细胞的增殖。信号通路分析表明，这三种成分可能靶向细胞凋亡、抗凋亡和细胞周期相关蛋白。这三种成分通过调节凋亡和抗凋亡蛋白，包括 B 细胞淋巴瘤-2 和全长和裂解聚（ADP-核糖）聚合酶蛋白的表达，诱导细胞凋亡。它们还诱导 A549 细胞的细胞周期停滞在 S 和 G2/M 期，并诱导自噬。
麦冬汤成分对肺癌的药理机制可能与其对细胞凋亡、自噬、细胞周期进展和细胞增殖的调节作用密切相关。
