Ursolic acid inhibits cigarette smoke extract-induced human bronchial epithelial cell injury and prevents development of lung cancer

Molecules. 2012 Aug 2;17(8):9104-15. doi: 10.3390/molecules17089104.

Abstract

Cigarette smoking is the main cause of chronic obstructive pulmonary disease and lung cancer. The present study was aimed to explore the chemopreventive effect of ursolic acid (UA) on these diseases. In the CSE treated normal human bronchial epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the intracellular redox balance, and relieved the stimulation of external deleterious factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. Moreover, UA inhibited lung cancer development in the model established by A549 cells in nude mice in vivo. For the first time, our results indicate that UA could be developed as a potential lung cancer chemopreventive agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Bronchioles / pathology*
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cells, Cultured
  • Chemoprevention
  • Cyclophosphamide / pharmacology
  • Cytoprotection
  • DNA Damage
  • Epithelial Cells / drug effects*
  • Epithelial Cells / enzymology
  • Epithelial Cells / pathology
  • Glutathione / metabolism
  • Glutathione Transferase / metabolism
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Lung Neoplasms / etiology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Metabolic Detoxication, Phase II
  • Mice
  • Mice, Nude
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Nicotiana / adverse effects*
  • Smoke / adverse effects*
  • Triterpenes / pharmacology*
  • Tumor Burden / drug effects
  • Ursolic Acid
  • Xenograft Model Antitumor Assays

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents, Alkylating
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Smoke
  • Triterpenes
  • Cyclophosphamide
  • L-Lactate Dehydrogenase
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Glutathione Transferase
  • Glutathione