Stobadine inhibits doxorubicin-induced apoptosis through a caspase-9 dependent pathway in P815 mastocytoma cells.
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).
Bağriaçik
E Ümit
EÜ
Gazi University, Faculty of Medicine, Department of Immunology, Ankara, Turkey.
Uslu
Kadriye
K
Yurtçu
Erkan
E
Stefek
Milan
M
Karasu
Cimen
C
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology*; D053453:Caspase 9 / Q000378:metabolism*; D061945:Caspase Inhibitors; D004317:Doxorubicin / Q000494:pharmacology*; D034801:Mastocytoma / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D009336:Necrosis
D000975:Antioxidants; D002243:Carbolines; D061945:Caspase Inhibitors; D004317:Doxorubicin; D053453:Caspase 9; D000111:Acetylcysteine; C100106:dicarbine