Stobadine inhibits doxorubicin-induced apoptosis through a caspase-9 dependent pathway in P815 mastocytoma cells

Cell Biol Int. 2007 Sep;31(9):979-84. doi: 10.1016/j.cellbi.2007.03.008. Epub 2007 Mar 18.

Abstract

Doxorubicin (DOXO), a widely used chemotherapeutic agent, induces apoptosis in transformed and non-transformed cells. The apoptotic effect of DOXO has been linked to the generation of reactive oxygen species (ROS). Antioxidants may be effective in the prevention of DOX-induced apoptosis. In the present study we investigated the effects of stobadine, a pyridoindole antioxidant in a DOXO-induced apoptosis model of P815 cells by flow cytometric analyses and by measuring caspase-3 and caspase-9 activities. Pretreating cells with stobadine significantly increased cell viability and decreased apoptosis rate. Inhibition in apoptosis was observed at maximum levels following treatment of cells with 10(-7)M stobadine as evident from flow cytometric analyses. The antiapoptotic effect of stobadine was further confirmed by inhibition of caspase-3 and caspase-9 activities. We found that the antioxidative effects of stobadine were comparable to the effects of a well known antioxidant, N-acetyl l-cysteine (NAC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Carbolines / pharmacology*
  • Caspase 9 / metabolism*
  • Caspase Inhibitors
  • Doxorubicin / pharmacology*
  • Mastocytoma / enzymology*
  • Mastocytoma / pathology*
  • Mice
  • Necrosis

Substances

  • Antioxidants
  • Carbolines
  • Caspase Inhibitors
  • Doxorubicin
  • Caspase 9
  • Acetylcysteine
  • dicarbine