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

Phytomedicine. 2019 May;58:152893. doi: 10.1016/j.phymed.2019.152893. Epub 2019 Mar 13.

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.

Keywords: Apoptosis; Chinese herbal medicine; Lung cancer; Natural compound; Network analysis.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chalcones / pharmacology
  • Drug Screening Assays, Antitumor / methods*
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Chalcones
  • Drugs, Chinese Herbal
  • maimendongtang
  • licochalcone A