A Two-complementary Method Assay for Screening New Reversal Agents of Cancer Cell Multidrug Resistance

Abstract

Multidrug resistance represents a major obstacle in the successful therapy of neoplastic diseases. P-Glycoprotein appears to play an important role in such cells by acting as an energy-dependent efflux pump which removes various natural drugs from the cell before they had any chance to exert their cytotoxic effects. In the present study, a twomethod assay based on the direct interaction with a purified C -terminal recombinant cytosolic domain of P-glycoprotein and the increase of intracellular daunomycin in a multidrug resistant cell line has been adapted for the screening and detection of potential inhibitors of P-glycoprotein present in various plant extracts. This paper demonstrates that the two methods are simple and sensitive, and constitute quantitative tools to assess the capacity of complex samples such as plant extracts to inhibit P-glycoprotein transporters; they also are useful for screening or identifying new inhibitors of Pglycoprotein.