ArticleBioFactors (Oxford, England)2018
Efflux excretion of bisdemethoxycurcumin-O-glucuronide in UGT1A1-overexpressing HeLa cells: Identification of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 (MRP1) as the glucuronide transporters.
Article in BioFactors (Oxford, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 8 citations in OpenAlex.
- Impact of Training Data, Ground Truth and Shape Variability in the Deep Learning-Based Semantic Segmentation of HeLa Cells Observed with Electron Microscopy.Journal of imaging · 2023Article
- Characterization of metabolic activity, isozyme contribution and species differences of bavachin, and identification of efflux transporters for bavachin-O-glucuronide in HeLa1A1 cells.The Journal of pharmacy and pharmacology · 2020Article
- Potential metabolism determinants and drug-drug interactions of a natural flavanone bavachinin.RSC advances · 2020Article
- Study on mechanism of elemene reversing tumor multidrug resistance based on luminescence pharmacokinetics in tumor cellsRSC advances · 2020Article
- Metabolism and disposition of corylifol A fromXenobiotica; the fate of foreign compounds in biological systems · 2020Article
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9 authors at 3 institutions in 3 countries.
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Abstract
Bisdemethoxycurcumin (BDMC) was a natural curcuminoid with many bioactivities present in turmeric (Curcuma longa L.). However, the disposition mechanisms of BDMC via uridine 5'-diphospho-glucuronosyltransferase (UGT) metabolism still remain unclear. Therefore, we aimed to determine the potential efflux transporters for the excretion of BDMC-O-glucuronide. Herein, chemical inhibition assays (Ko143, MK571, dipyridamole, and leukotriene C4) and biological inhibition experiments including stable knocked-down of breast cancer resistance protein (BCRP), multidrug resistance-associated proteins (MRPs) transporters were both performed in a HeLa cell line stably overexpressing UGT1A1 established previously. The results indicated that Ko143 (5 and 20 μM) caused a marked reduction in excretion rate (18.4-55.6%) and elevation of intracellular BDMC-O-glucuronide (28.8-48.1%), whereas MK-571 (5 and 20 μM) resulted in a significant decrease in excretion rate (6.2-61.6%) and increase of intracellular BDMC-O-glucuronide (maximal 27.1-32.6%). Furthermore, shRNA-mediated silencing of BCRP transporter led to a marked reduction in the excretion rate (21.1-36.9%) and an obvious elevation of intracellular glucuronide (24.9%). Similar results were observed when MRP1 was partially silenced. In addition, MRP3 and MRP4 silencing both displayed no obvious changes on the excretion rate and intracellular levels of glucuronide. In conclusion, chemical inhibition and gene silencing results both indicated that generated BDMC-O-glucoside were excreted primarily by the BCRP and MRP1 transporters. © 2018 BioFactors, 44(6):558-569, 2018.
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