Cellular Models and In Vitro Assays for the Screening of modulators of P-gp, MRP1 and BCRP

• Type: Another Publication in an International Scientific Journal
• Date: 2017

Authors

Gameiro, M (Author) Other; Silva, R (Author) Other; Rocha Pereira, C (Author) Other; Helena Carmo (Author) FFUP; Felix Carvalho (Author) FFUP; Maria de Lourdes Bastos (Author) FFUP; Fernando Remiao (Author) FFUP

Journal

Title: Molecules

Vol. 22

Final page: 600

ISSN: 1420-3049

Publisher: MDPI

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 50 Citations

Other information

Authenticus ID: P-00M-V3K

DOI: 10.3390/molecules22040600

Abstract (EN): Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are highly expressed in tumor cells, as well as in organs involved in absorption and secretion processes, mediating the ATP-dependent efflux of compounds, both endogenous substances and xenobiotics, including drugs. Their expression and activity levels are modulated by the presence of inhibitors, inducers and/or activators. In vitro, ex vivo and in vivo studies with both known and newly synthesized P-glycoprotein (P-gp) inducers and/or activators have shown the usefulness of these transport mechanisms in reducing the systemic exposure and specific tissue access of potentially harmful compounds. This article focuses on the main ABC transporters involved in multidrug resistance [P-gp, multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)] expressed in tissues of toxicological relevance, such as the blood-brain barrier, cardiovascular system, liver, kidney and intestine. Moreover, it provides a review of the available cellular models, in vitro and ex vivo assays for the screening and selection of safe and specific inducers and activators of these membrane transporters. The available cellular models and in vitro assays have been proposed as high throughput and low-cost alternatives to excessive animal testing, allowing the evaluation of a large number of compounds.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 48