Reactive oxygen species and antioxidants in apoptosis of esophageal cancer cells induced by As2O3

Int J Mol Med. 2003 Apr;11(4):479-84.

Abstract

To explore the relationship between the reactive oxygen species (ROS) and apoptosis in esophageal carcinoma cells (SHEE85) induced by arsenic trioxide (As2O3), we focused on changes of apoptosis, ROS, and antioxidants. Apoptosis of SHEE85 was confirmed by means of DNA fragmentation stained by Hoechst 33342, Sub-G1 cells scored by flow cytometry and ultrastructure of cells by electron microscopy. To evaluate the level of ROS, the chemiluminescent method was used for measuring the production of superoxide anion (O(-)*2). Lipid peroxide (malondialdehyde, MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured respectively by the photometry method. In the cells treated with As2O3 at a concentration of 5.0 micromol/l for 2-24 h, the content of cellular O(-)*2 and MDA was increased, but SOD and GSH-Px were significantly lower in the process of apoptosis in SHEE85. As2O3 at concentration of 0.5 micromol/l did not cause cell apoptosis but promoted cell proliferation. These results suggest that As2O3 at a high dosage (5 micromol/l) causes cell apoptosis and at a low dosage (0.5 micromol/l) causes cell proliferation. The essential mechanisms of cell apoptosis induced by As2O3 may be related to the increase of ROS and decrease of anti-oxidation. ROS and antioxidants participate in the apoptotic pathway of esophageal carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Cell Cycle / drug effects
  • DNA Fragmentation / drug effects
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / ultrastructure
  • Humans
  • Microscopy, Electron
  • Oxides / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Arsenicals
  • Oxides
  • Reactive Oxygen Species
  • Arsenic Trioxide