We propose that the cellular burden of certain carcinogens may be mitigated by P-glycoprotein (P-gp), the putative drug effiux pump. In a series of multidrug resistant human breast cancer MCF-7 cells with increasing P-gp expression we examined this hypothesis using benzo(a)pyrene, a widely distributed environmental and dietary carcinogen. We found that multidrug resistant cells were cross-resis...

The multidrug resistance gene product P-glycoprotein (P-GP) was assessed immunohistochemically (by antibody JSB-1) in biopsy specimens from 27 oesophageal squamous carcinomas and 10 adenocarcinomas before treatment with mitomycin, ifosfamide and cisplatin (MIC). Tumours were assessed following treatment and correlation with response sought. Of the squamous carcinomas, 74% (20/27) responded to M...

Overexpression of P-glycoprotein (P-gp), a plasma membrane transporter which extrudes chemotherapeutic agents out of cells, has been associated with the multidrug resistance (MDR) of cancer cells. It has been revealed that flavonoids and other polyphenols inhibit P-gp activity. Due to their inhibitory activities of polyphenols on P-gp function and their physiological safety, they are possible c...

The multidrug resistance P-glycoprotein (P-gp) was recently proposed to redistribute cholesterol in the plasma membrane, suggesting that P-gp could modulate cholesterol efflux to cholesterol acceptors. To address this hypothesis and to reevaluate the role of P-gp in cholesterol homeostasis, we first analyzed the role of P-gp expression on cholesterol efflux in P-gp stably transfected drug-selec...

The objective of this study was to quantitatively examine the protein expression of relevant transporters and other proteins in the brain capillary endothelial cells isolated from wild-type mice and P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and P-gp/Bcrp knockout mice. After the isolation of brain capillary endothelial cells, a highly sensitive liquid chromatography-tandem...

We propose that the cellular burden of certain carcinogens may be mitigated by P-glycoprotein (P-gp), the putative drug effiux pump. In a series of multidrug resistant human breast cancer MCF-7 cells with increasing P-gp expression we examined this hypothesis using benzo(a)pyrene, a widely distributed environmental and dietary carcinogen. We found that multidrug resistant cells were cross-resis...

Inhibition of drug efflux pumps such as P-glycoprotein (P-gp) is an approach toward combating multidrug resistance, which is a significant hurdle in current cancer treatments. To address this, N-substituted aryloxymethyl pyrrolidines were designed and synthesized in their homochiral forms in order to investigate the stereochemical requirements for the binding site of P-gp. Our study provides ev...

OBJECTIVES To evaluate the role of P-glycoprotein (P-gp) and multidrug-resistant-protein 1 (MRP1) on raltegravir intracellular drug disposition in CD4+ T cells, investigate the effect of HIV-1 infection on P-gp expression and correlate HIV-1 viraemia with P-gp activity in primary CD4+ T cell subsets. METHODS The cellular accumulation ratio of [(3)H]raltegravir was quantified in CD4+ T cell li...

BACKGROUND Permeability glycoprotein (P-glycoprotein or P-gp) plays an important role in the intestinal absorption of the immunosuppressive agents: cyclosporine and tacrolimus. OBJECTIVES The aim of this study was to determine how the intestinal absorption of cyclosporine and tacrolimus is affected when they are used with P-gp activating or inhibiting agents. MATERIAL AND METHODS In in vitr...

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expressi...