scholarly journals Epigenetic Regulation of Multidrug Resistance Protein 1 and Breast Cancer Resistance Protein Transporters by Histone Deacetylase Inhibition

2020 ◽  
Vol 48 (6) ◽  
pp. 459-480 ◽  
Author(s):  
Dahea You ◽  
Jason R. Richardson ◽  
Lauren M. Aleksunes
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Histone Deacetylase ◽  
Breast Cancer Resistance Protein ◽  
Multidrug Resistance Protein ◽  
Cancer Resistance ◽  
Multidrug Resistance Protein 1 ◽  
Histone Deacetylase Inhibition ◽  
Resistance Protein ◽  
Protein Transporters

Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Mediate the Disposition of Leonurine-10-O-β-glucuronide

2020 ◽  
Vol 21 (13) ◽  
pp. 1060-1067
Author(s):  
Xiaocui Li ◽  
Yushan Xie ◽  
Wei Qu ◽  
Xiaojun Ou ◽  
Xiaowen Ou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Gene Knockout ◽  
Multidrug Resistance Protein ◽  
Cancer Resistance ◽  
Wild Type ◽  
Multidrug Resistance Protein 2 ◽  
Intestinal Microsomes ◽  
Resistance Protein

Background: Leonurine (Leo), a promising antilipemic agent that has been approved for clinical trials, is extensively metabolized into bioactive Leonurine-10-O-β-glucuronide (L-10-G) vivo. Objective: To explore the effects of breast cancer resistance protein (Bcrp) and multidrug resistance protein 2 (Mrp2) on the disposition of L-10-G. Methods: The pharmacokinetics, tissue distribution and intestinal perfusion of Leo were studied by using efflux transporter gene knockout mouse models. The enzyme kinetics via liver and intestinal microsomes were also examined. Results: After intravenous injection with Leo, the AUC0-∞ values of L-10-G in Bcrp1-/- and Mrp2-/- mice were 1.55-fold and 16.80-fold higher, respectively, than those in wild-type FVB mice (P < 0.05). After oral administration, the AUC0-∞ value of L-10-G showed a 2.82-fold increase in Mrp2-/- mice compared with wild-type FVB mice (P < 0.05). After gavage with Leo for 10 and 25 min, the bile accumulation of L-10-G in Mrp2-/- mice was 3-fold and 22-fold lower, respectively, than that in wild-type FVB mice (P < 0.05). Besides, the intestinal excreted amount of L-10-G showed 2.22-fold and 2.68-fold decrease in Bcrp1-/- and Mrp2-/- mice, respectively, compared with that in wild-type FVB mice (P < 0.05). The clearance of L-10-G decreased in liver microsomes and increased in intestinal microsomes of Bcrp1-/- and Mrp2-/- mice compared to the wild-type FVB mice (P < 0.05). Conclusion: Both Bcrp and Mrp2 are involved in the disposition of L-10-G, and Mrp2 exhibits a superior influence.

scholarly journals Uremic Toxins Inhibit Transport by Breast Cancer Resistance Protein and Multidrug Resistance Protein 4 at Clinically Relevant Concentrations

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18438 ◽  
Author(s):  
Henricus A. M. Mutsaers ◽  
Lambertus P. van den Heuvel ◽  
Lauke H. J. Ringens ◽  
Anita C. A. Dankers ◽  
Frans G. M. Russel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Uremic Toxins ◽  
Multidrug Resistance Protein ◽  
Cancer Resistance ◽  
Resistance Protein
Sign in / Sign up

Export Citation Format

Share Document