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