THE INFLUENCE OF GLUTATHIONE METABOLISM ON MULTIDRUG-RESISTANCE IN MRP-OVEREXPRESSING CELLS

The multidrug resistance ((+)associated) protein (MRP) is one of two A TP-dependent transport molecules which have been shown to be a cause o f multidrug resistance in mammalian cells,The protein is ubiquitously expressed in human tissues and in a range of tumor types. In addition to a range of neutral or cationic cytotoxic drugs, MRP also transports heavy metals and organic anions including glutathione (GSH)-conjugate s and glucuronate conjugates. In cells depleted of GSH, the activity o f MRP towards cationic drugs is abrogated whereas activity towards org anic anions is preserved. Possible mechanisms involved in this differe ntial action and strategies for its exploitation in clinical chemother apy are discussed.