alexa A new generation of MDR modulating agents with dual activity: P-gp inhibitor and iNOS inducer agents.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Colabufo NA, Contino M, Berardi F, Perrone R, Panaro MA,

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Abstract MultiDrug Resistance (MDR) is due to the ability of some ATPase transporters to efflux chemotherapeutic agents out from tumor cells decreasing the endocellular concentration for the pharmacological effect, causing cancer cells chemoresistance. In the present work, a set of MDR modulating agents (MC89, MC70, PB28, IG9) able to modulate transmembrane ATP-dependent transporter, P-glycoprotein (P-gp), and also to induce inducible nitric oxide synthase (iNOS) expression in a panel of tumor cell lines are presented. All selected compounds, known as potent P-gp modulating agents, stimulated nitric oxide (NO) via iNOS in U937, Caco-2 and MCF7-Adr cell lines. The results displayed a new pharmacological strategy to revert MDR and lead to develop a new class of MDR reverting agents devoid of the limits of P-gp inhibitors third generation. Copyright © 2010 Elsevier Ltd. All rights reserved. This article was published in Toxicol In Vitro and referenced in Journal of Bioequivalence & Bioavailability

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