Genistein and Glyceollin Effects on ABCC2 (MRP2) and ABCG2 (BCRP) in Caco-2 Cells

Abstract

The goal of the present study was to determine the effects of glyceollins on intestinal ABCC2 (ATP Binding Cassette C2, multidrug resistance protein 2, MRP2) and ABCG2 (ATP Binding Cassette G2, breast cancer resistance protein, BCRP) function using the Caco-2 cell intestinal epithelial cell model. Glyceollins are soy-derived phytoestrogens that demonstrate anti-proliferative activity in several sources of cancer cells. 5 (and 6)-carboxy-2′,7′-dichloroflourescein (CDF) was used as a prototypical MRP2 substrate; whereas BODIPY-prazosin provided an indication of BCRP function. Comparison studies were conducted with genistein. Glyceollins were shown to inhibit MRP2-mediated CDF transport, with activity similar to the MRP2 inhibitor, MK-571. They also demonstrated concentration-dependent inhibition BCRP-mediated efflux of BODIPY-prazosin, with a potency similar to that of the recognized BCRP inhibitor, Ko143. In contrast, genistein did not appear to alter MRP2 activity and even provided a modest increase in BCRP efflux of BODIPY-prazosin. In particular, glyceollin inhibition of these two important intestinal efflux transporters suggests the potential for glyceollin to alter the absorption of other phytochemicals with which it might be co-administered as a dietary supplement, as well as alteration of the absorption of pharmaceuticals that may be administered concomitantly.

Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats

“…The aim of the study was first to investigate whether BDL altered the expression and function of BCRP in the brains of rats by using Western blotting and assessment of the concentration of prazosin, which is a typical substrate of BCRP [30][31][32][33] , respectively, and then to identify components in BDL rat serum that affected BCRP function and expression, by using human cerebral microvessel endothelial cells (HCMEC/D3) and Madin-Darby canine kidney cells expressing human BCRP (MDCK-BCRP) as in vitro models. Additionally, the contribution of UCB to the altered function and expression of BCRP in the brain by BDL was further investigated by both in vitro and in vivo studies.…”

Cancer chemoprevention through dietary flavonoids: what’s limiting?

“…A recent report indicated that some flavonoids (e.g., genistein and glyceollin) also interact with other ABC transporters such as ABCC2 (MRP2) [138]. In addition, certain flavonoids are substrates for ABC transporters, thereby limiting their absorption from the gastrointestinal tract, distribution to body tissues and organs, and, ultimately, their bioavailability [139].…”

San-Huang-Xie-Xin-Tang Constituents Exert Drug-Drug Interaction of Mutual Reinforcement at Both Pharmacodynamics and Pharmacokinetic Level: A Review

“…In-vitro research on the efflux pump and ITs normally use Caco-2 cell or MDCK cell for they both have similar structure of differential intestinal epithelial cell with apical side and basolateral side (Chen et al, 2013; Schexnayder and Stratford, 2015; Obringer et al, 2016). Currently, it is verified that Bai from RS is the substrate of both MRP2 and BCRP (Kalapos-Kovács et al, 2015), and another RS constituent Bae is also pumped out by MRP (Zhang et al, 2007).…”