Vimentin Protects Cells Against Doxorubicin and Vincristine

Abstract

Vimentin is a class III IF protein that among other functions in the cells interacts with mitochondria causing the elevation of their membrane potential. This interaction may be very important although they are still poorly understood. In this study vimentin-null cells and derivative cell lines that express different mutant forms of human vimentin were used as a model to investigate the ability of this protein to provide the resistance of cells against antitumor drugs and its dependence on the interaction with mitochondria. The half maximal inhibitory concentration (IC₅₀) of vincristine and doxorubicin, two commonly used anticancer drugs, demonstrated that drug resistance of the cells increases only with the vimentin forms that can bind mitochondria. Mutant forms of vimentin lacking the ability to bind mitochondria had no effect on drug resistance. The effect of vimentin on cell viability was observed in the presence of verapamil, the inhibitor of P-glycoprotein, product of Multi-Drug Resistance (MDR) gene. We propose that the interaction of mitochondria with vimentin protects and stabilizes these organelles in the stress conditions.