Induction of multidrug resistance P-glycoprotein
inhibits the antiapoptotic action of mitochondria-targeted antioxidant SkQR1
E.K. Fetisova, M.P. Valichov, D.S. Izumov, B.V. Chernyak
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University
Mitochondria-targeted antioxidants of the SkQ 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 reactive oxygen species. 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 K- 562 cells, it was found that the subline sensitive to chemotherapy is protected by SkQR1 from apoptotic action of oxidative stress. Protection of the resistant subline occurs only after inhibition of P-glycoprotein.
Homo Sapiens Liberatus Workshop, Moscow State University, May 2010