The role of reactive oxygen species (ROS) production on diallyl disulfide (DADS) induced apoptosis and cell cycle arrest in human A549 lung carcinoma cells

Mutat Res. 2005 Nov 11;579(1-2):115-24. doi: 10.1016/j.mrfmmm.2005.02.026. Epub 2005 Jul 18.

Abstract

Diallyl disulfide (DADS), an oil soluble constituent of garlic (Allium sativum), has been reported to cause antimutagentic and anticarcinogenic effects in vitro and in vivo by modulating phases I and II enzyme activities. In recent years, several studies suggested that the chemopreventive effects of DADS can also be attributed to induction of cell cycle arrest and apoptosis in cancer cells. In the present study, we reported that DADS-induced cell cycle arrest at G2/M and apoptosis in human A549 lung cancer cells in a time- and dose-dependent manner. Additionally, a significant increase of intracellular reactive oxygen species (ROS) was induced in A549 cells less than 0.5h after DADS treatment, indicating that ROS may be an early event in DADS-modulated apoptosis. Treatment of A549 cells with N-acetyl cysteine (NAC) completely abrogated DADS-induced cell cycle arrest and apoptosis. The result indicated that oxidative stress modulates cell proliferation and cell death induced by DADS.

MeSH terms

  • Acetylcysteine / pharmacology
  • Allyl Compounds / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Cell Cycle / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disulfides / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Reactive Oxygen Species / metabolism*
  • Tumor Cells, Cultured

Substances

  • Allyl Compounds
  • Antineoplastic Agents
  • Antioxidants
  • Disulfides
  • Reactive Oxygen Species
  • diallyl disulfide
  • Acetylcysteine