Search results for "Transporter"
showing 10 items of 676 documents
Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells.
2015
Abstract Background: The antihypertensive reserpine is an indole alkaloid from Rauwolfia serpentina and exerts also profound activity against cancer cells in vitro and in vivo. The present investigation was undertaken to investigate possible modes of action to explain its activity toward drug-resistant tumor cells. Material and methods: Sensitive and drug-resistant tumor cell lines overexpressing P-glycoprotein (ABCB1/MDR1), breast cancer resistance protein (ABCG2/BCRP), mutation-activated epidermal growth factor receptor (EGFR), wild-type and p53-knockout cells as well as the NCI panel of cell lines from different tumor origin were analyzed. Reserpine's cytotoxicity was investigated by res…
Selective downregulation of the MDR1 gene product in Caco-2 cells by stable transfection to prove its relevance in secretory drug transport.
2005
Considerable interest is focused on overcoming multidrug resistance (MDR) in cancer chemotherapy. The in vitro experiments to characterize P-glycoprotein's (P-gp) function and to decrease its effects have led to a variety of strategies such as addition of competitors or supplementation of the medium with oligonucleotides complementary to the 5'-end of the MDR1-mRNA. For the Caco-2 cell line, an in vitro model for absorption screening, expressing multiple transporters including P-gp, which pumps substances back into the apical solution, P-gp activity might mask other relevant transport proteins' activity. The objective of the present study was to construct a Caco-2 subline with reduced P-gp …
Pharmacogenomic Characterization of Cytotoxic Compounds from Salvia officinalis in Cancer Cells.
2015
Salvia officinalis is used as a dietary supplement with diverse medicinal activity (e.g. antidiabetic and antiatherosclerotic effects). The plant also exerts profound cytotoxicity toward cancer cells. Here, we investigated possible modes of action to explain its activity toward drug-resistant tumor cells. Log10IC50 values of two constituents of S. officinalis (ursolic acid, pomolic acid) were correlated to the expression of ATP-binding cassette (ABC) transporters (P-glycoprotein/ABCB1/MDR1, MRP1/ABCC1, BCRP/ABCG2) and epidermal growth factor receptor (EGFR) or mutations in RAS oncogenes and the tumor suppressor gene TP53 of the NCI panel of cell lines. Gene expression profiles predicting se…
Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics
2021
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Inhibition of ATP-Binding Cassette Transporters by Chinese Herbs and Phytochemicals
2012
The gene family of ATP-binding cassette (ABC) transporters is widely distributed over the evolutionary tree of life from bacteria to man. In cancer, several ABC transporters are involved in the transport of anticancer drugs. This leads to the development of resistance to a broad spectrum of anticancer agents, termed multidrug resistance. An attractive strategy to overcome multidrug resistance is to block the transport function of ABC transporters leading to lethal intracellular concentrations of anticancer drugs. Efforts to identify transport inhibitors lead to a huge amount of chemical substances, none of which successfully passed clinical trials in cancer patients because of high toxicity…
Cytotoxicity of cucurbitacin E from Citrullus colocynthis against multidrug-resistant cancer cells
2019
Abstract Background Cucurbitacin E (CuE) is an oxygenated tetracyclic triterpenoid isolated from the fruits of Citrullus colocynthis (L.) Schrad. Purpose This study outlines CuE's cytotoxic activity against drug-resistant tumor cell lines. Three members of ABC transporters superfamily, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and ABCB5 were investigated, whose overexpression in tumors is tightly linked to multidrug resistance. Further factors of drug resistance studied were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR). Methods Cytotoxicity assays (resazurin assays) were used to investigate the activity of Citrullus colocynthis and CuE towar…
Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix.
2012
Purpose: This study investigated the absorption mechanism of the phytochemicals indicaxanthin and betanin and the influence of their food matrix (cactus pear and red beet) on the intestinal transport. Methods: Trans-epithelial transport of dietary-consistent amounts of indicaxanthin and betanin in Caco-2 cell monolayers seeded on TranswellR inserts was measured in apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction, under an inwardly directed pH gradient (pH 6.0/7.4, AP/BL) mimicking luminal and serosal sides of human intestinal epithelium. The effect of inhibitors of membrane transporters on the absorption was also evaluated. Contribution of the paracellular route was…
A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people
2009
The T cell branch of the immune system has been extensively studied in the elderly and it is known that the elderly have impaired immune function, mainly due to the chronic antigenic load that ultimately causes shrinkage of the T cell repertoire and filling of the immunologic space with memory T cells. In the present paper, we describe the IgD(-)CD27(-) double-negative B cell population which (as we have recently described) is higher in the elderly. Most of these cells were IgG(+). Evaluation of the telomere length and expression of the ABCB1 transporter and anti-apoptotic molecule, Bcl2, shows that they have the markers of memory B cells. We also show that these cells do not act as antigen…
Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study
2021
Abstract Background The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, inten…
Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy…
2020
Anthracycline uptake could be affected by influx and efflux transporters in acute myeloid leukemia (AML). Combinations of single-nucleotide polymorphisms (SNPs) of wild-type genotype of influx transporters (SLC22A16, SLCO1B1) and homozygous variant genotypes of ABC polymorphisms (ABCB1, ABCC1, ABCC2, ABCG2) were evaluated in 225 adult de novo AML patients. No differences in complete remission were reported, but higher induction death was observed with combinations of SLCO1B1 rs4149056 and ABCB1 (triple variant haplotype, rs1128503), previously associated with ABCB1 and SLCO1B1 SNPs. Several combinations of SLCO1B1 and SLC22A16 with ABCB1 SNPs were associated with higher toxicities, includin…