Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress

Free Radic Biol Med. 2006 Sep 15;41(6):874-85. doi: 10.1016/j.freeradbiomed.2006.04.031. Epub 2006 May 10.

Abstract

Malignant mesothelioma cells differentiate into sarcomatoid or epithelioid phenotypes. The sarcomatoid cell type is more resistant to chemotherapy and gives a worse prognosis. We have investigated whether selenite alone and in combination with doxorubicin induced apoptosis in variously differentiated mesothelioma cells. Selenite in concentrations that could potentially be administered to patients strongly inhibited the growth of the sarcomatoid mesothelioma cells (IC50 = 7.5 microM), whereas epithelioid cells were more sensitive to doxorubicin. Benign mesothelial cells remained largely unaffected. Selenite potentiated doxorubicin treatment. Apoptosis was the dominating mode of cell death. The toxicity of selenite was mediated by oxidative stress. Furthermore the activity of the thioredoxin system was directly dependent on the concentration of selenite. This offers a possible mechanism of action of selenite treatment. Our findings suggest that selenite is a promising new drug for the treatment of malignant mesothelioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Glutathione Peroxidase / metabolism
  • Humans
  • Mesothelioma / pathology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Sodium Selenite / toxicity*
  • Sulfhydryl Compounds / metabolism

Substances

  • Sulfhydryl Compounds
  • Glutathione Peroxidase
  • Sodium Selenite