Vladimir M. Rzheznikov
Serbia
Research Article
Thiol - Dependent Sensitization of Mitochondria and Tumor Cells to Doxorubicin
Author(s): Nadezhda I Fedotcheva, Valeri A Bykov, Viktor V Banin, Tatyana A Fedotcheva, Vladimir M. Rzheznikov and Nikolai L ShimanovskiiNadezhda I Fedotcheva, Valeri A Bykov, Viktor V Banin, Tatyana A Fedotcheva, Vladimir M. Rzheznikov and Nikolai L Shimanovskii
The problem of multidrug resistance has been intensively studied during the last decade. It is known that some synthetic progestins can chemosensitize tumor cells to cytostatic drugs; however, the mechanisms of the sensitization are not clearly understood. In this study, the effect of synthetic analogue of progesterone (17α-acetoxy- 3b-butanoyloxy-6-methyl-pregna-4, 6-diene-20-on, buterol) on the survival of doxorubicin-resistant MCF-7 cells and the coupling of isolated mitochondria was investigated in comparison with the thiol reagent N-ethylmaleimide (NEM). Both compounds increased the doxorubicin-induced cell death and decreased the oxidative phosphorylation and the coupling in mitochondria; their presence was necessary for the direct action of doxorubicin on the mitochondrial membrane potential. Possible specific targets for NEM and buterol are the SH-groups of mitochondrial.. View More»
