Interplay of Breast Cancer Resistance Protein (BCRP) and Metabolizing Enzymes

Abstract

The recent identification of the interplay between metabolizing enzymes and BCRP has drawn more and more attention from people. BCRP, a transporter belonging to ATP-binding cassette (ABC) family, has been hypothesized to play roles in many aspects including protecting the human body against therapeutics because it is expressed in the tissues that function as barriers in vivo. Efficient coupling of BCRP and metabolizing enzymes enables rapid elimination of foreign compounds from the body because BCRP could facilitate the excretion of metabolites catalyzed by phase I and II enzymes into bile, urine and feces. Without BCRP coupling, pass through the cell membrane may be difficult for them by passive diffusion because of the increment of the molecular weight and water solubility. Thus the metabolism-efflux alliance has extraordinary importance to drug metabolism, distribution, pharmacological effect, toxicity and elimination. In this manuscript, a brief discussion about the interplays of BCRP and metabolizing enzymes in liver, intestine, kidney, lung and other organs were presented and summarized. Many endogenous and exogenous compounds belong to different chemical groups, for instance, the dietary flavonoids and the steroidal hormones were involved. Clarifying the cooperation mechanisms of BCRP and enzymes could lead to a better prediction of drug clearance in vitro.

Investigation of adrenal and thyroid gland dysfunction in dogs with ultrasonographic diagnosis of gallbladder mucocele formation

“…It should also be considered that dogs with gallbladder mucocele formation could have an impaired excretion of DHEAS. DHEAS is transported by organic anion-transporting polypeptide (OATP) family members[61], ABCG2[62], and likely other efflux transporters[63] that play critical roles in excretion of endogenous compounds and xenobiotics. In particular, ABCG2 (aka Breast Cancer Resistance Protein, BCRP) resides in the hepatocyte canalicular membrane[62] and many ABCG2 substrates, including DHEAS, are products of phase II metabolism by co-expressed sulfotransferases.…”

“…In particular, ABCG2 (aka Breast Cancer Resistance Protein, BCRP) resides in the hepatocyte canalicular membrane[62] and many ABCG2 substrates, including DHEAS, are products of phase II metabolism by co-expressed sulfotransferases. In the absence of ABCG2 activity these compounds can be increased in plasma and reduced in bile[63]. It is of interest that a number of compounds excreted by ACBG2, such as phytoestrogens[64] and riboflavin[65], were identified in a previous study to be significantly lower in the bile of dogs with gallbladder mucocele formation compared to control dogs[66].…”

The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids

“…Breast cancer–resistance protein, organic anion transporting polypeptide, and, in particular, organic anion transporters 1 and 3 that are expressed in basolateral membranes of renal tubules and couple with phase I and phase II metabolism are thought to be important facets of the elimination process (28, 50–52). The overexpression of organic anion transporter is associated with more-efficient renal uptake and elimination into the urine (51).…”

Metabolism of Curcumin in Human Breast Cancer Cells: Impact of Sulfation on Cytotoxicity

“…Curcumin sulfate concentration in the cellular medium was up to 12-fold higher compared to the cytoplasm, indicating a not yet identified active transport system for this metabolite. A likely candidate for the cellular transport into the medium is the breast cancer resistance protein (BCRP, ABCG2), which is distributed in several tissues, such as placenta, small intestine, colon, and the hepatic canalicular membrane, but also in breast ductal cells, and plays an important role in the efflux of sulfated conjugates of steroids and xenobiotics [21]. Interaction of curcumin with BCRP has already been documented and may also apply to its sulfate [22].…”