title: Assessing multidrug resistance protein 1-mediated function in cancer cell multidrug resistance by scanning electrochemical microscopy and flow cytometry.
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(2)OH) and its oxidized form ([FcCH(2)OH](+)) affect the redox state of cancer cells. Specifically, the interaction of FcCH(2)OH 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(2)OH in multidrug-resistant cells is in part due to MRP1's unspecific efflux. Scanning electrochemical microscopy confirmed the interaction between FcCH(2)OH and the cells, and the differential response was observed to depend on MRP1 expression. This newly established relation between FcCH(2)OH/[FcCH(2)OH](+), GSH/GSSG and multidrug resistance in human cancer cells enables than the acquisition of scanning electrochemical microscopy images.
authors.affiliation: Laboratory for Electrochemical Reactive Imaging and Detection for Biological Systems, Department of Chemistry, Université du Québec à Montréal, Canada.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kuss
authors.forename: Renaud
authors.initials: R
authors.lastname: Cornut
authors.forename: Isabelle
authors.initials: I
authors.lastname: Beaulieu
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Mezour
authors.forename: Borhane
authors.initials: B
authors.lastname: Annabi
authors.forename: Janine
authors.initials: J
authors.lastname: Mauzeroll
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D055664:Electrochemical Techniques / Q000379:methods*; D005296:Ferrous Compounds / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008853:Microscopy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005296:Ferrous Compounds; C071550:ferrocenemethanol; D005978:Glutathione; D019803:Glutathione Disulfide