Chemical inhibition and stable knock-down of efflux transporters leads to reduced glucuronidation of wushanicaritin in UGT1A1-overexpressing HeLa cells: the role of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in the excretion of glucuronides.

@article{Qin2018ChemicalIA,
  title={Chemical inhibition and stable knock-down of efflux transporters leads to reduced glucuronidation of wushanicaritin in UGT1A1-overexpressing HeLa cells: the role of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in the excretion of glucuronides.},
  author={Zifei Qin and Shishi Li and Zhihong Yao and X. Hong and Baojian Wu and K. Krausz and F. Gonzalez and Hao Gao and X. Yao},
  journal={Food \& function},
  year={2018},
  volume={9 3},
  pages={
          1410-1423
        }
}
Active efflux transport of glucuronides out of cells is a critical process in elimination of drugs and food-derived compounds. Wushanicaritin, a natural polyphenol from Epimedium species, has shown many biological activities. However, the transporters responsible for excretion of wushanicaritin glucuronides still remain undefined. Herein, chemical inhibitors (Ko143, MK571, dipyridamole and leukotriene C4) and single stable knocked-down efflux transporters (BCRP, MRP1, MRP3 and MRP4) were used… Expand
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Mechanism of the efflux transport of demethoxycurcumin-O-glucuronides in HeLa cells stably transfected with UDP-glucuronosyltransferase 1A1
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References

SHOWING 1-10 OF 47 REFERENCES
Stable knock-down of efflux transporters leads to reduced glucuronidation in UGT1A1-overexpressing HeLa cells: the evidence for glucuronidation-transport interplay.
TLDR
Celluluronidation was significantly altered by decreasing expression of efflux transporters, revealing a strong interplay of glucuronidation with efflux transport. Expand
UDP-Glucuronosyltransferase (UGT) 1A9-Overexpressing HeLa Cells Is an Appropriate Tool to Delineate the Kinetic Interplay between Breast Cancer Resistance Protein (BRCP) and UGT and to Rapidly Identify the Glucuronide Substrates of BCRP
TLDR
The engineered HeLa cells stably overexpressing UGT1A9 is an appropriate model to study the kinetic interplay between UGT 1A9 and BCRP in the phase II disposition of flavonoids and should also be very useful to rapidly identify whether a phase II metabolite is the substrate of B CRP. Expand
Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodin.
TLDR
UGT is a main metabolic pathway for emodin in the intestine, and the MRP family is composed of major efflux transporters responsible for the excretion of emodIn glucuronide in the intestines. Expand
Characterization of Chrysin Glucuronidation in UGT1A1-Overexpressing HeLa Cells: Elucidating the Transporters Responsible for Efflux of Glucuronide
TLDR
Chemical inhibition indicated that excretion of CG was contributed by the MRP family transporters, whereas the role of BCRP was unclear, and gene silencing results suggested that B CRP, MRP1, MRp3, and MRP4 were significant contributors to excretion. Expand
Efflux transport of chrysin and apigenin sulfates in HEK293 cells overexpressing SULT1A3: The role of multidrug resistance-associated protein 4 (MRP4/ABCC4).
Efflux transport is a critical determinant to the pharmacokinetics of sulfate conjugates. Here we aimed to establish SULT1A3 stably transfected HEK293 cells, and to determine the contributions ofExpand
Decreased Expression of Multidrug Resistance-Associated Protein 4 (MRP4/ABCC4) Leads to Reduced Glucuronidation of Flavonoids in UGT1A1-Overexpressing HeLa Cells: The Role of Futile Recycling.
TLDR
In conclusion, futile recycling was involved in cellular glucuronidation, accounting for transporter-dependent glucuronidated of flavonoids. Expand
Sulfonation of raloxifene in HEK293 cells overexpressing SULT1A3: Involvement of breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 4 (MRP4/ABCC4) in excretion of sulfate metabolites.
TLDR
Sulfonation of raloxifene and excretion of its sulfate metabolites were investigated using SULT1A3-overexpressing HEK293 cells with significant expression of BCRP and MRP4 with significant decreases in the CLef,app values. Expand
Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C.
TLDR
A new tetracyclic analogue of FTC, Ko143, is evaluated as a practical inhibitor of BCRP, proving highly active for increasing the intracellular drug accumulation and reversing Bcrp1/BCRP-mediated multidrug resistance. Expand
Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport.
TLDR
Evidence is provided of the ability of MRP to transport cysteinyl leukotriene C4 in membrane vesicles from MRP-transfected HeLa cells (T14), as well as drug-selected H69AR lung cancer cells which express high levels of MRp. Expand
Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
TLDR
Characterization of the UGT1A locus and genetic studies directed at understanding the role of bilirubin glucuronidation and the biochemical basis of the clinical symptoms found in unconjugated hyperbilirubinemia have uncovered the structural gene polymorphisms associated with Crigler-Najjar's and Gilbert's syndrome. Expand
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