Abstract
Cancer cell multidrug resistance is a molecular signature that highly influences the outcome of chemotherapy treatment and for which there is currently no robust method to monitor in vitro its activity. Herein, we demonstrate that ferrocenemethanol (FcCH 2OH) and its oxidized form ([FcCH 2OH] +) affect the redox state of cancer cells. Specifically, the interaction of FcCH 2OH with the glutathione couple (GSH/GSSG) is shown in human adenocarcinoma cervical cancer cells HeLa and a multidrug resistant variant overexpressing the multidrug resistant associated protein 1 (MRP1) using bioanalytical techniques, such as flow cytometry and fluorescence microscopy. It is further demonstrated that the differential response to FcCH 2OH in multidrug-resistant cells is in part due to MRP1's unspecific efflux. Scanning electrochemical microscopy confirmed the interaction between FcCH 2OH and the cells, and the differential response was observed to depend on MRP1 expression. This newly established relation between FcCH 2OH/[FcCH 2OH] +, GSH/GSSG and multidrug resistance in human cancer cells enables than the acquisition of scanning electrochemical microscopy images.
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