scholarly journals Quantitative Analysis of the ABCG2 c.421C > A Polymorphism Effect on In Vivo Transport Activity of Breast Cancer Resistance Protein (BCRP) Using an Intestinal Absorption Model

2015 ◽  
Vol 104 (9) ◽  
pp. 3039-3048 ◽  
Author(s):  
Yuta Tanaka ◽  
Yoshiaki Kitamura ◽  
Kazuya Maeda ◽  
Yuichi Sugiyama
Keyword(s):  
Breast Cancer ◽  
Quantitative Analysis ◽  
Intestinal Absorption ◽  
Breast Cancer Resistance Protein ◽  
Absorption Model ◽  
Cancer Resistance ◽  
Transport Activity ◽  
Resistance Protein

scholarly journals Modulation of Placental Breast Cancer Resistance Protein by HDAC1 in Mice: Implications for Optimization of Pharmacotherapy During Pregnancy

2021 ◽  
Author(s):  
Chuan Wang ◽  
Dan Ma ◽  
Yimin Hua ◽  
Hongyu Duan
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Negative Control ◽  
Great Promise ◽  
Cancer Resistance ◽  
Gene Expressions ◽  
Time Curve ◽  
Resistance Protein

AbstractBreast cancer resistance protein (BCRP/ABCG2) is a critical drug efflux transporters by limiting drugs’ transplacental transfer rates. More investigations on the regulation of placental BCRP offer great promise for enabling pronounced progress in individualized and safe pharmacotherapy during pregnancy. Histone deacetylases (HDACs) play an important role in epigenetic regulation of placental genes. It was reported recently by us that HDAC1 was involved in placental BCRP regulation in vitro. The aim of this study was to further explore the effect of HDAC1 on placental BCRP expression and functionality in animals. Randomly assigned C57BL pregnant dams received intraperitoneal injections of a negative control siRNA or Hdac1 siRNA from embryonic day 7.5 (E7.5) to E15.5, respectively. At E16.5, glyburide (GLB), a probe for evaluating placental BCRP efflux functionality, was injected via the tail vein. Animals were sacrificed through cervical dislocation at various times (5–180 min) after drug administration. The maternal blood, placentas, and fetal-units were collected. GLB concentrations were determined by a validated high-performance liquid chromatography/mass spectrometry (HPLC-MS) assay. Real-time quantitative PCR (qRT-PCR), Western blot, and immunohistochemical (IHC) analysis were employed to identify mRNA/protein levels and localization of gene expressions, respectively. It was noted that Hdac1 inhibition significantly decreased placental Bcrp expression, with markedly increases of GLB concentrations and area under the concentration-time curve (AUC) in fetal-units. Particularly, the ratios of fetal-unit/maternal plasma GLB concentrations were also significantly elevated following Hdac1 repression. Taken together, these findings suggested that HDAC1 was involved in positive regulation of placental BCRP expression and functionality in vivo.

scholarly journals Quercetin Is a Flavonoid Breast Cancer Resistance Protein Inhibitor with an Impact on the Oral Pharmacokinetics of Sulfasalazine in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 397
Author(s):  
Yoo-Kyung Song ◽  
Jin-Ha Yoon ◽  
Jong Kyu Woo ◽  
Ju-Hee Kang ◽  
Kyeong-Ryoon Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cancer Resistance ◽  
Concentration Dependent Manner ◽  
Resistance Protein

The potential inhibitory effect of quercetin, a major plant flavonol, on breast cancer resistance protein (BCRP) activity was investigated in this study. The presence of quercetin significantly increased the cellular accumulation and associated cytotoxicity of the BCRP substrate mitoxantrone in human cervical cancer cells (HeLa cells) in a concentration-dependent manner. The transcellular efflux of prazosin, a stereotypical BCRP substrate, was also significantly reduced in the presence of quercetin in a bidirectional transport assay using human BCRP-overexpressing cells; further kinetic analysis revealed IC50 and Ki values of 4.22 and 3.91 μM, respectively. Moreover, pretreatment with 10 mg/kg quercetin in rats led to a 1.8-fold and 1.5-fold increase in the AUC8h (i.e., 44.5 ± 11.8 min∙μg/mL vs. 25.7 ± 9.98 min∙μg/mL, p < 0.05) and Cmax (i.e., 179 ± 23.0 ng/mL vs. 122 ± 23.2 ng/mL, p < 0.05) of orally administered sulfasalazine, respectively. Collectively, these results provide evidence that quercetin acts as an in vivo as well as in vitro inhibitor of BCRP. Considering the high dietary intake of quercetin as well as its consumption as a dietary supplement, issuing a caution regarding its food–drug interactions should be considered.

scholarly journals Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies

2018 ◽  
Vol 19 (10) ◽  
pp. 3165 ◽  
Author(s):  
Yang Liu ◽  
Li Guo ◽  
Mire Zloh ◽  
Yujuan Zhang ◽  
Jinhu Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Mdck Cells ◽  
Binding Pocket ◽  
Chicken Breast ◽  
Pharmacokinetic Studies ◽  
Cancer Resistance ◽  
Resistance Protein

Florfenicol (FFC) is a valuable synthetic fluorinated derivative of thiamphenicol widely used to treat infectious diseases in food animals. The aims of the study were to investigate whether FFC is a substrate for the breast cancer resistance protein (BCRP) and whether the transporter influences oral availability of FFC. In vitro transport assays using MDCK-chAbcg2 cells were conducted to assess chicken BCRP-mediated transport of FFC, while in vivo pharmacokinetic experiments with single or combined BCRP inhibitor gefitinib were employed to study the role of BCRP in oral FFC disposition. According to U.S. Food and Drug Administration (FDA) criteria, FFC was found to be a potential BCRP substrate due to the net efflux ratio being over 2.0 (2.37) in MDCK cells stably transfected with chicken BCRP and the efflux completely reversed by a BCRP inhibitor (Gefitinib). The molecular docking results indicated that florfenicol can form favorable interactions with the binding pocket of homology modeled chicken BCRP. Pharmacokinetic studies of FFC in different aged broilers with different expression levels of BCRP showed that higher BCRP expression would cause a lower Area Under Curve (AUC) and a higher clearance of FFC. In addition, more extensive absorption of florfenicol after the co-administration with gefitinib (a BCRP inhibitor) was observed. The overall results demonstrated that florfenicol is a substrate of the chicken breast cancer resistant protein which in turn affects its pharmacokinetic behavior.

scholarly journals Breast Cancer Resistance Protein and P-Glycoprotein Influence In Vivo Disposition of 11C-Erlotinib

2015 ◽  
Vol 56 (12) ◽  
pp. 1930-1936 ◽  
Author(s):  
A. Traxl ◽  
T. Wanek ◽  
S. Mairinger ◽  
J. Stanek ◽  
T. Filip ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Resistance Protein

Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin In Vivo and Vitro

2015 ◽  
Vol 30 (4) ◽  
pp. 218-225 ◽  
Author(s):  
Jin-hua Wen ◽  
Xiao-hua Wei ◽  
Xiang-yuan Sheng ◽  
De-qing Zhou ◽  
Hong-wei Peng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ursolic Acid ◽  
Breast Cancer Resistance Protein ◽  
Cancer Resistance ◽  
Resistance Protein
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