The influence of glutathione metabolism on multidrug resistance in MRP-overexpressing cells.
The multidrug resistance (+associated) protein (MRP) is one of two ATP-dependent transport molecules which have been shown to be a cause of 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)-conjugates and glucuronate conjugates. In cells depleted of GSH, the activity of MRP towards cationic drugs is abrogated whereas activity towards organic anions is preserved. Possible mechanisms involved in this differential action and strategies for its exploitation in clinical chemotherapy are discussed.
Twentyman
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United Kingdom Co-ordinating Committee on Cancer Research, London, UK. p.twentyman@icrf.icnet.uk
Bagrij
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T