Arsenic trioxide (As(2)O(3)) induced apoptosis and its mechanisms in a human esophageal squamous carcinoma cell line

Chin Med J (Engl). 2002 Feb;115(2):280-5.

Abstract

Objective: To study whether As(2)O(3) has an apoptotic effect on human solid tumor cells, and the possible cellular and molecular mechanisms of this treatment using human esophageal squamous carcinoma cells (EC8712) as a model.

Methods: DNA microarray, biochemical and cytological analyses were used.

Results: The growth and survival of EC8712 cells were markedly inhibited by As(2)O(3) treatment at a concentration of 1, 2 and 4 micromol/L. EC8712 cells were obviously arrested at G2/M phase with As(2)O(3) treatment and apoptosis induced at micromolar As(2)O(3) concentrations, as shown by morphology, histogram related nuclear DNA contents, and DNA gel electrophoresis. As(2)O(3) activated caspase-3, which might be involved in the process of As(2)O(3), induced apoptosis in EC8712 cells.

Conclusions: As(2)O(3) changes the expression of many genes at transcription level. The regulation of expression of many genes might be involved in the process of As(2)O(3) inducing apoptosis. These results suggest that As(2)O(3) can be clinically useful for solid tumor treatment.

MeSH terms

  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Microscopy, Electron
  • Oxides / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / ultrastructure

Substances

  • Arsenicals
  • Oxides
  • Arsenic Trioxide