Reactive oxygen species and mitochondrial membrane potential are modulated during CDDP-induced apoptosis in EC-109 cells

Biochem Cell Biol. 2007 Apr;85(2):265-71. doi: 10.1139/O07-014.

Abstract

cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Deltapsim), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Deltapsim; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Deltapsim are events involved in the apoptotic pathway of EC-109 induced by CDDP.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Catalase / pharmacology
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Humans
  • Membrane Potential, Mitochondrial / drug effects*
  • Mitochondria / metabolism*
  • Reactive Oxygen Species / metabolism*

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Catalase
  • Cisplatin