MULTIDRUG RESISTANCE P-GLYCOPROTEIN INHIBITS THE ANTIAPOPTOTIC ACTION
OF MITOCHONDRIA-TARGETED ANTIOXIDANT SkQR1
E. K. Fetisova,1 A. V. Avetisyan, D. S. Izumov, M. V. Korotetskaya, V. N. Tashlitsky,
V. P. Skulachev, B. V. Chernyak
A. N. Belozersky Institute of Physico-Chemical Biology of Moscow State University;
1 e-mail: fetis@belozersky.msu.ru
Mitochondria-targeted antioxidants of the SkQR1 family, being accumulated in energized mitochondria,
protect cells from oxidative stress by increasing the level of reduced glutathione and decreasing the cell-damaging
effect induced by hydrogen peroxide. Using various human transformed cell lines and SkQR1 (a fluorescent
member of the SkQ family), we show that SkQR1 is ejected from chemotherapy-resistant cells by P-glycoprotein
— one of the main transport proteins determining multidrug resistance typical for many neoplastic
cells. It is also shown that SkQR1 ejection is neutralized by P-glycoprotein inhibitors (verapamil and pluronic
L61). In experiments on K562 cells, it was found that the subline sensitive to chemotherapy is protected by
SkQR1 from apoptotic action of hydrogen peroxide. Protection of the resistant subline occurs only after inhibition
of P-glycoprotein.
Key words: mitochondrion, antioxidants, oxidative stress, multidrug resistance, P-glycoprotein, SkQ
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