Inhibition of multidrug resistance related protein by acetyl salicylic acid in cultured human lung cells

Abstract

BACKGROUND: Multidrug resistance related proteins (MRP-proteins), members of the ATP binding cassette (ABC-) superfamily, are known to play an important role in regulation of glutathione homeostasis within cells, and hence in GSH dependent transport processes of xenobiotics. Many airborne compounds are hazardous inducing inflammatory reactions in lung and are suspected to play a substantial role in initiation and/or promotion of tumor formation. It is interesting to clarify whether and how anti-prostaglandins modify MRP function in normal human lung cells. Aspirin, an acetylated salicylate, is classified among the non-steroidal anti-inflammatory drugs (NSAIDs), reduce inflammatory signs and symptoms exhibiting a broad range of pharmacological activities (analgesic, antipyretic and antiplatelet properties). Cyclooxygenase (COX)-system catalyses the rate limiting step in prostanoids (prostaglandin (PG)) synthesis and is also involved in drug resistance and poor prognosis of many neoplastic diseases. Aspirin's ability to suppress prostaglandins and thromboxanes production is due to its irreversible inactivation of the cyclo-oxygenase (COX) enzyme. Furthermore, transport activity study of MRP1 in NHBEC, PLC and A549 under the effect of exogenously supplied PGE2 showed an increased activity. METHODOLOGY and RESULTS: In this study, both the localisation and description of the cellular distribution of MRP-1 under standard culture conditions in normal human bronchial epithelial cells (NHBEC), peripheral lung cells (PLC) and tumor lung cells (A549) was proved using indirect immunofluorescence microscopy. All substrates and incubation periods have been pre-checked for cellular toxicity in the MTT assay in order to guarantee that non toxic conditions are applied. CONCLUSION: COX inhibitor (acetylsalicylic acid 1,2mM) could significantly decrease the transport activity of MRP1 in NHBEC, PLC and A549 in 1 and 3 days trials.