Absolute immunoquantification of the expression of ABC transporters P-glycoprotein, breast cancer resistance protein and multidrug resistance-associated protein 2 in human liver and duodenum

2012 ◽  
Vol 83 (2) ◽  
pp. 279-285 ◽  
Author(s):  
Theodora G.H.A. Tucker ◽  
Alison M. Milne ◽  
Sylvie Fournel-Gigleux ◽  
Katherine S. Fenner ◽  
Michael W.H. Coughtrie
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Abc Transporters ◽  
Human Liver ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Resistance Protein

Enniatin B1 is a substrate of intestinal P-glycoprotein, multidrug resistance-associated protein 2 and breast cancer resistance protein

2010 ◽  
Vol 3 (3) ◽  
pp. 271-281 ◽  
Author(s):  
L. Ivanova ◽  
S. Uhlig ◽  
G. Eriksen ◽  
L. Johannessen
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Apical Direction ◽  
Resistance Protein ◽  
First Time ◽  
Fumitremorgin C ◽  
Absorption Characteristics

Enniatins are cyclic hexadepsipeptides produced by various fungi, known to have ionophoric, antibiotic and insecticidal activity. The aim of the present study was to evaluate the intestinal absorption characteristics of enniatin B1 (ENN-B1). Using the human intestinal Caco-2 cell line, we found that the permeability of ENN-B1 in the basolateral to apical direction was 6.7× higher as compared to the permeability in the opposite direction, indicating involvement of apically located transporters. Transport of ENN-B1 in the apical to basolateral direction was increased significantly upon treatment of Caco-2 cells with the P-glycoprotein (Pgp) inhibitor verapamil and the multidrug resistance-associated protein 2 (MRP2) inhibitor MK571, but only weakly and not significantly after treatment with the breast cancer resistance protein (BCRP) inhibitor fumitremorgin C. Additionally, MDCK II cells over-expressing Pgp, MRP2 or BCRP, showed reduced sensitivity towards ENN-B1. These data demonstrate for the first time that ENN-B1 is a substrate of MRP2 and suggests that Pgp, MRP2 and possibly BCRP are involved in transport of ENN-B1 across the intestine.

scholarly journals Interactions of retinoids with the ABC transporters P-glycoprotein and Breast Cancer Resistance Protein

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Szabolcs Tarapcsák ◽  
Gábor Szalóki ◽  
Ágnes Telbisz ◽  
Zsuzsanna Gyöngy ◽  
Krisztina Matúz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Abc Transporters ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Resistance Protein

scholarly journals Tyrosine and aurora kinase inhibitors diminish transport function of multidrug resistance-associated protein (MRP) 4 and breast cancer resistance protein (BCRP)

ADMET & DMPK ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 302
Author(s):  
Rhiannon N. Hardwick ◽  
Marina Snellings ◽  
Brian C. Ferslew ◽  
Yang Lu ◽  
Kim L.R. Browuer
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Abc Transporters ◽  
Breast Cancer Resistance Protein ◽  
Kinase Inhibitors ◽  
Efflux Transporters ◽  
Atp Binding ◽  
Cancer Resistance ◽  
Sulfate Uptake ◽  
Resistance Protein

<p class="PaperKeywordTitle">Tyrosine and aurora kinases are important effectors in signal transduction pathways that are often involved in aberrant cancer cell growth. Tyrosine (TKI) and aurora (AKI) kinase inhibitors are anti-cancer agents specifically designed to target such signaling pathways through TKI/AKI binding to the ATP-binding pocket of kinases thereby leading to diminished kinase activity. Some TKIs have been identified as inhibitors of ATP-binding cassette (ABC) transporters such as P-glycoprotein and breast cancer resistance protein (BCRP), which are commonly upregulated in malignant cells. TKI/AKIs have been investigated as ABC transporter inhibitors in order to facilitate the accumulation of concomitantly administered chemo-therapeutics within cancer cells. However, ABC transporters are prominently expressed in the liver and other eliminating organs, and their inhibition has been linked to intracellular accumulation of drugs, altered disposition, and toxicity. The potential for TKIs/AKIs to inhibit other important hepatic efflux transporters, particularly multidrug resistance-associated proteins (MRPs), remains unknown. The aim of the current study was to compare the inhibitory potency of 20 selected TKI/AKIs against MRP4 and BCRP through the use of inverted membrane vesicle assays. Relative IC<sub>50 </sub>values were estimated by determining TKI/AKI inhibition of MRP4-mediated [<sup>3</sup>H]-dehydroepiandrosterone sulfate uptake and BCRP-mediated [<sup>3</sup>H]-estrone sulfate uptake. To provide insight to the clinical relevance of TKI/AKI inhibition of ABC efflux transporters, the ratio of the steady-state maximum total plasma concentration (C<sub>ss</sub>) to the IC<sub>50</sub> for each compound was calculated with C<sub>ss</sub>/IC<sub>50</sub> ratio &gt;0.1 deemed potentially clinically relevant. Such analysis identified several potentially clinically relevant inhibitors of MRP4: alisertib, danusertib, erlotinib, lapatinib, neratinib, nilotinib, pazopanib, sorafenib, and tozasertib. The potentially clinically relevant inhibition of BCRP was much more extensive and included alisertib, barasertib, danusertib, enzastaurin, erlotinib, gefitinib, imatinib, neratinib, nilotinib, pazopanib, selumetinib, sorafenib, sunitinib, tozasertib, and vandetanib. These findings indicate the significant potential for TKI/AKIs to inhibit multiple ABC efflux transporters. The resulting inhibition data could provide insight regarding the clinical interpretation of pharmacokinetic/pharmacodynamic outcomes when TKI/AKIs are administered concomitantly with additional chemotherapeutic agents.</p>

scholarly journals Effect of GenX on P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance–Associated Protein 2 at the Blood–Brain Barrier

2020 ◽  
Vol 128 (3) ◽  
pp. 037002 ◽  
Author(s):  
Ronald E. Cannon ◽  
Alicia C. Richards ◽  
Andrew W. Trexler ◽  
Christopher T. Juberg ◽  
Birandra Sinha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Blood Brain Barrier ◽  
Breast Cancer Resistance Protein ◽  
Brain Barrier ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Resistance Protein
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