Modulation of P-glycoprotein efflux pump: induction and activation as a therapeutic strategy

• Type: Another Publication in an International Scientific Journal
• Date: 2015

Authors

Renata Silva (Author) Other; Vania Vilas Boas (Author) Other; Helena Carmo (Author) FFUP; Ricardo Jorge Dinis Oliveira (Author) FMUP; Felix Carvalho (Author) FFUP; Maria de Lourdes Bastos (Author) FFUP; Fernando Remiao (Author) FFUP

Journal

Title: PHARMACOLOGY & THERAPEUTICS

Vol. 149

Pages: 1-123

ISSN: 0163-7258

Publisher: Pergamon Press - Elsevier

Indexing

ISI Web of Knowledge - 195 Citations

Scopus - 214 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-00A-9HB

DOI: 10.1016/j.pharmthera.2014.11.013

Abstract (EN): P-glycoprotein (P-gp) is an ATP-dependent efflux pump encoded by the MDRI gene in humans, known to mediate multidrug resistance of neoplastic cells to cancer therapy. For several decades, P-gp inhibition has drawn many significant research efforts in an attempt to overcome this phenomenon. However, P-gp is also constitutively expressed in normal human epithelial tissues and, due to its broad substrate specificity, to its cellular polarized expression in many excretory and barrier tissues, and to its great efflux capacity, it can play a crucial role in limiting the absorption and distribution of harmful xenobiotics, by decreasing their intracellular accumulation. Such a defense mechanism can be of particular relevance at the intestinal level, by significantly reducing the intestinal absorption of the xenobiotic and, consequently, avoiding its access to the target organs. In this review, the current knowledge on this important efflux pump is summarized, and a new focus is brought on the therapeutic interest of inducing and/or activating P-gp for limiting the toxicity caused by its substrates. Several in vivo and in vitro studies validating the use of such a therapeutic strategy are discussed. An extensive literature search for reported P-gp inducers/activators and for the experimental models used in their characterization was conducted. Those studies demonstrate that effective antidotal pathways can be achieved by efficiently promoting the P-gp-mediated efflux of deleterious xenobiotics, resulting in a significant reduction in their intracellular levels and, consequently, in a significant reduction of their toxicity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 123