The Impact of Breast Cancer Resistance Protein (BCRP/ABCG2) on Drug Transport Across Caco-2 Cell Monolayers

Abstract

The impact of breast cancer resistant protein (BCRP/ABCG2) on drug transport across Caco-2 cell monolayers

Characterization of P-Glycoprotein Inhibitors for Evaluating the Effect of P-Glycoprotein on the Intestinal Absorption of Drugs

“…Caco-2 cells from Dainippon Sumitomo Pharma (Osaka, Japan) were cultured in DMEM supplemented with 10% heat-inactivated fetal bovine serum, 1% antibiotic-antimycotic, 1% nonessential amino acids, and 2 mM L-glutamine [31]. Cells were maintained at 37 • C in 5% CO 2 /95% air and passaged upon reaching approximately 80% confluence using 0.25% trypsin/1 mM EDTA solution.…”

“…The apical-to-basal (AP-to-BL) P app value (P app,AB ) (•), and basal-to-apical (BL-to-AP) P app value (P app,BA ) ( ) values were determined by the AP-to-BL and BL-to-AP transport of paclitaxel in Caco-2 cells in the presence or absence of various concentrations of P-gp inhibitors. The P app,BA values of paclitaxel in the presence of GF120918, LY335979, and WK-X-34 were cited from our previous report [31]. Data are represented as mean ± S.D.…”

Feature, Function, and Information of Drug Transporter–Related Databases

“…There are three kinds of variability of DT abundances: (1) organism-specific expressions (Durmus et al, 2015), (2) tissue-differential distributions (Nixon et al, 2016) and ( 3) disease-dependent abundances (Evers et al, 2018). As provided in Table 2, the tissue-differential distribution data have been provided by multiple databases, such as TTD, PharmGKB, UCSF-FDA TransPortal, Metrabase and VARIDT, which further demonstrate the critical roles of such variability in drug disposition (Kawahara et al, 2020). For the remaining two kinds of variability data, VARIDT is the only knowledge base of such information, and the differential expression patterns are provided for 108 diseases and 3 model organisms.…”

“…Membrane transporters play critical roles in discovering new drugs and elucidating disease mechanisms (Nigam, 2018), which can be divided into channels, carriers, electron flow carriers, group translocators, and pumps for determining the molecular composition and energy state of cells (Cook et al, 2014;Saier et al, 2021). The identified drug uptake/efflux transporters may constitute only a small fraction of all these general transporters, but these general transporters are of great importance for elucidating drug metabolism (Wang et al, 2020b) and disposition (Kawahara et al, 2020). Thus, the databases available for describing general transporters and transporter families are valuable treasures for current DT research.…”

“…Particularly, the data regarding DT's expression, distribution and function demonstrate its disease-differential expression (Evers et al, 2018), organism-dependent abundance (Durmus et al, 2015), tissue-specific distribution (Nixon et al, 2016), transporting functional family (Shen et al, 2017), and so on; the data of epigenetic modification on DT describe the DNA/histone methylation & acetylation (Liu et al, 2016), non-coding RNA regulation (Yu et al, 2019), and so on; the data of DT's conformation and structural variations involve species-specific evolution (Dias and Sa-Correia, 2014), the structures of the entire transporter (Penmatsa et al, 2013) and functional conserved/substrate-binding domain (Xue et al, 2016), and so on; the data of DT's exogenous regulation discuss the clinical drug-drug interactions (Kosa et al, 2018), regulatory substrate, inhibitor & inducer (Muller et al, 2018), and so on; the data describing DT's genetic polymorphisms provide the cytogenetic locations (Lewis and Girisha, 2020), disease indication induced by hereditary factor (Karimian et al, 2020), genetic variant & frequency (Veldic et al, 2019), and so on. The above knowledge is valuable for understanding the drug ADME process (Nigam, 2015;Ye et al, 2019), which is thus essential for current research on drug metabolism (Li et al, 2020b;Wang et al, 2020a;He et al, 2021) and disposition (Bai et al, 2016;Kawahara et al, 2020). However, such valuable knowledge is largely dispersed in the literature, which hampers its utility and significantly limits its possibility for comprehensive analysis (Li et al, 2018b;Yang et al, 2020b).…”