Anti-proliferative Effect of Physcion on Human Gastric Cell Line via Inducing ROS-Dependent Apoptosis

Cell Biochem Biophys. 2015 Nov;73(2):537-543. doi: 10.1007/s12013-015-0674-9.

Abstract

In this study, the anti-proliferative effect of physcion, an anthraquinone derivative isolated and characterized from both terrestrial and marine sources, against human gastric cancer SGC-7901 cells was investigated and the underlying mechanisms were explored. Physcion reduced SGC-7901 cell viability in a dose- and time-dependent manner, as demonstrated by MTT assay. It triggered the mitochondrial/caspase apoptotic pathway indicated by loss of mitochondrial membrane potential and cytochrome c release. Moreover, physcion induced a sustained activation of the phosphorylation of AMPK, and compound C (an inhibitor of AMPK) significantly reversed physcion-induced apoptosis in SGC-7901 cells. In addition, physcion provoked the generation of reactive oxygen species (ROS) in SGC-7901 cells, while the antioxidant N-acetyl cysteine almost completely blocked physcion-induced AMPK activation and apoptosis. Taken together, these findings suggest that physcion induces apoptosis through a ROS/AMPK-dependent mitochondrial pathway.

Keywords: AMPK; Apoptosis; Gastric cancer; ROS.

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / metabolism
  • Acetylcysteine / pharmacology
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cytochromes c / metabolism
  • Emodin / analogs & derivatives*
  • Emodin / toxicity
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Phosphorylation / drug effects
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • Reactive Oxygen Species
  • Cytochromes c
  • AMP-Activated Protein Kinases
  • Caspase 3
  • physcione
  • Emodin
  • Acetylcysteine