7,583 results match your criteria p-glycoprotein activity

QTMP, a Novel Thiourea Polymer, Causes DNA Damage to Exert Anticancer Activity and Overcome Multidrug Resistance in Colorectal Cancer Cells.

Front Oncol 2021 28;11:667689. Epub 2021 May 28.

School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.

Colorectal cancer (CRC) is one of the most common malignancies, and multidrug resistance (MDR) severely restricts the effectiveness of various anticancer drugs. Therefore, the development of novel anticancer drugs for the treatment of CRC patients with MDR is necessary. Quaternized thiourea main-chain polymer (QTMP) is a self-assembled nanoparticle with good water solubility. Read More

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Medicinal chemistry of anthranilic acid derivatives: A mini review.

Drug Dev Res 2021 Jun 12. Epub 2021 Jun 12.

Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab, India.

Anthranilic acid and its analogues present a privileged profile as pharmacophores for the rational development of pharmaceuticals deliberated for managing the pathophysiology and pathogenesis of various diseases. The substitution on anthranilic acid scaffold provides large compound libraries, which enable a comprehensive assessment of the structure activity relationship (SAR) analysis for the identification of hits and leads in a typical drug development paradigm. Besides, their widespread applications as anti-inflammatory fenamates, the amide and anilide derivatives of anthranilic acid analogues play a central role in the management of several metabolic disorders. Read More

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Transporter-interfering chemicals inhibit P-glycoprotein of yellowfin tuna (Thunnus albacares).

Comp Biochem Physiol C Toxicol Pharmacol 2021 Jun 8;248:109101. Epub 2021 Jun 8.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0202, United States of America. Electronic address:

Marine pollutants bioaccumulate at high trophic levels of marine food webs and are transferred to humans through consumption of apex species. Yellowfin tuna (Thunnus albacares) are marine predators, and one of largest commercial fisheries in the world. Previous studies have shown that yellowfin tuna can accumulate high levels of persistent organic pollutants, including Transporter Interfering Chemicals (TICs), which are chemicals shown to bind to mammalian xenobiotic transporters and interfere with their function. Read More

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Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system.

Sci Rep 2021 Jun 3;11(1):11670. Epub 2021 Jun 3.

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Caco-2 cells are widely used as an in vitro intestinal epithelial cell model because they can form a monolayer and predict drug absorption with high accuracy. However, Caco-2 cells hardly express cytochrome P450 (CYP), a drug-metabolizing enzyme. It is known that CYP3A4 is the dominant drug-metabolizing enzyme in human small intestine. Read More

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Multiple strategies with the synergistic approach for addressing colorectal cancer.

Biomed Pharmacother 2021 May 31;140:111704. Epub 2021 May 31.

Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt. Electronic address:

Cancer treatment is improving widely over time, but finding a proper defender to beat them seems like a distant dream. The quest for identification and discovery of drugs with an effective action is still a vital work. The role of a membrane protein called P-glycoprotein, which functions as garbage chute that efflux the waste, xenobiotics, and toxins out of the cancer cells acts as a major reason behind the therapeutic failure of most chemotherapeutic drugs. Read More

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Insight into Bortezomib Focusing on Its Efficacy against P-gp-Positive MDR Leukemia Cells.

Int J Mol Sci 2021 May 23;22(11). Epub 2021 May 23.

Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, Slovakia.

In this paper, we compared the effects of bortezomib on L1210 (S) cells with its effects on P-glycoprotein (P-gp)-positive variant S cells, which expressed P-gp either after selection with vincristine (R cells) or after transfection with a human gene encoding P-gp (T cells). Bortezomib induced the death-related effects in the S, R, and T cells at concentrations not exceeding 10 nM. Bortezomib-induced cell cycle arrest in the G2/M phase was more pronounced in the S cells than in the R or T cells and was related to the expression levels of cyclins, cyclin-dependent kinases, and their inhibitors. Read More

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Essential Oils, and , Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein.

Nutrients 2021 May 19;13(5). Epub 2021 May 19.

Université de Bourgogne Franche-Comté, F-21000 Dijon, France.

The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, (PC) and Desf. Read More

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Curcumin at Low Doses Potentiates and at High Doses Inhibits ABT-737-Induced Platelet Apoptosis.

Int J Mol Sci 2021 May 20;22(10). Epub 2021 May 20.

Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany.

Curcumin is a natural bioactive component derived from the turmeric plant , which exhibits a range of beneficial activities on human cells. Previously, an inhibitory effect of curcumin on platelets was demonstrated. However, it is unknown whether this inhibitory effect is due to platelet apoptosis or procoagulant platelet formation. Read More

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Designing potent inhibitors against the multidrug resistance P-glycoprotein.

J Biomol Struct Dyn 2021 Jun 1:1-13. Epub 2021 Jun 1.

Department of Physical Sciences, University of Arkansas-Fort Smith, Fort Smith, Arkansas, USA.

The multidrug transporter P-glycoprotein is an ATP binding cassette (ABC) exporter responsible for resistance to tumor cells during chemotherapy. This study was designed with computational approaches aimed at identifying the best potent inhibitors of P-glycoprotein. Although many compounds have been suggested to inhibit P-glycoprotein, however, their information on bioavailability, selectivity, ADMET properties, and molecular interactions has not been revealed. Read More

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A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells.

Sci Rep 2021 May 24;11(1):10822. Epub 2021 May 24.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.

The success of cancer chemotherapy is limited by multidrug resistance (MDR), which is mainly caused by P-glycoprotein (P-gp) overexpression. In the present study, we describe a novel microtubule inhibitor, 5-(N-methylmaleimid-3-yl)-chromone (SPC-160002), that can be used to overcome MDR. A synthetic chromone derivative, SPC-160002, showed a broad spectrum of anti-proliferative effects on various human cancer cells without affecting P-gp expression and its drug efflux function. Read More

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Jatrophane diterpenoids as multidrug resistance modulators from Euphorbia sororia.

Bioorg Chem 2021 Jul 13;112:104989. Epub 2021 May 13.

State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China; The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, PR China. Electronic address:

Eight new jatrophane diterpenoids, Euphosorophane F-M (1-8), as well as fourteen known jatrophane diterpenoids (9-22) were separated and purified from the fructus of Euphorbia sororia, and the chemical structures were determined based on extensive spectroscopic analysis, 1D, 2D NMR and HRESIMS data included. Their absolute configurations of compounds 1, 2, 9, and 22 were elucidated by X-ray crystallographic analysis. These jatrophane diterpenoids showed lower cytotoxicity and compounds 3, 4, 11, 12, 13, 14, and 20 revealed promising multidrug resistance (MDR) reversal ability as modulators compared to verapamil (VRP) by MTT assay. Read More

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Overexpression of P-glycoprotein and MRP-1 are pharmacogenomic biomarkers to determine steroid resistant phenotype in childhood idiopathic nephrotic syndrome.

Pharmacogenomics J 2021 May 19. Epub 2021 May 19.

Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Steroid remains the keystone therapy for Idiopathic Nephrotic Syndrome (NS). Besides genetic factors and histological changes, pharmacogenomic factors also affect the steroid response. The upregulation of P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP-1) modulate the pharmacokinetics of steroids and may contribute to steroid resistance. Read More

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Curcumin reverses doxorubicin resistance in colon cancer cells at the metabolic level.

J Pharm Biomed Anal 2021 Jul 7;201:114129. Epub 2021 May 7.

Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Co-innovation Center of Henan Province for New Drug R&D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, China. Electronic address:

Doxorubicin (Dox) is commonly used for the treatment of malignant tumors, including colon cancer. However, the development of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in tumor chemotherapy has seriously reduced the therapeutic efficacy of Dox. Natural product curcumin (Cur) was demonstrated to have a variety of pharmacological effects, such as anti-tumor, anti-oxidation and anti-aging activities. Read More

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Effects of self-assembled cell-penetrating peptides and their nano-complexes on ABCB1 expression and activity.

Iran J Basic Med Sci 2021 Mar;24(3):383-390

Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Objectives: Doxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B1 (ABCB1) gene. Read More

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Relation between ABCB1 overexpression and COX2 and ALOX5 genes in human erythroleukemia cell lines.

Prostaglandins Other Lipid Mediat 2021 Aug 8;155:106553. Epub 2021 May 8.

Laboratório de Cultura Celular, ICB, FURG, RS, Brazil; Programa de Pós-Graduação em Ciências Fisiológicas, ICB, FURG, RS, Brazil. Electronic address:

This study aimed to characterize the relationship between the COX2 and ALOX5 genes, as well as their link with the multidrug resistance (MDR) phenotype in sensitive (K562) and MDR (K562-Lucena and FEPS) erythroleukemia cells. For this, the inhibitors of 5-LOX (zileuton) and COX-2 (acetylsalicylic acid-ASA) and cells with the silenced ABCB1 gene were used. The treatment with ASA caused an increase in the gene expression of COX2 and ABCB1 in both MDR cell lines, and a decrease in the expression of ALOX5 in the FEPS cells. Read More

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Subcellular distribution of ezrin/radixin/moesin and their roles in the cell surface localization and transport function of P-glycoprotein in human colon adenocarcinoma LS180 cells.

PLoS One 2021 11;16(5):e0250889. Epub 2021 May 11.

Laboratory of Clinical Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, Japan.

The ezrin/radixin/moesin (ERM) family proteins act as linkers between the actin cytoskeleton and P-glycoprotein (P-gp) and regulate the plasma membrane localization and functionality of the latter in various cancer cells. Notably, P-gp overexpression in the plasma membrane of cancer cells is a principal factor responsible for multidrug resistance and drug-induced mutagenesis. However, it remains unknown whether the ERM proteins contribute to the plasma membrane localization and transport function of P-gp in human colorectal cancer cells in which the subcellular localization of ERM has yet to be determined. Read More

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Exploiting the metabolic energy demands of drug efflux pumps provides a strategy to overcome multidrug resistance in cancer.

Biochim Biophys Acta Gen Subj 2021 Aug 12;1865(8):129915. Epub 2021 May 12.

Human Disease and Membrane Transport Laboratory, Division of Biomedical Science & Biochemistry, Research School of Biology and Medical School, The Australian National University, Canberra 2601, Australia. Electronic address:

Background: P-glycoprotein (P-gp) is a prevalent resistance mediator and it requires considerable cellular energy to ensure ATP dependent efflux of anticancer drugs. The glycolytic pathway generates the majority of catabolic energy in cancer cells; however, the high rates of P-gp activity places added strain on its inherently limited capacity to generate ATP. This is particularly relevant for compounds such as verapamil that are believed to trap P-gp in a futile transport process that requires continuing ATP consumption. Read More

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The study of Raddeanin A cerebrovascular endothelial cell trafficking through P-glycoprotein.

Biochem Biophys Res Commun 2021 Jun 4;559:222-229. Epub 2021 May 4.

Key Laboratory of Traditional Chinese Medicine Analysis, School of Pharmaceutical Sciences, Changchun University of Traditional Chinese Medicine, Changchun, 130117, China. Electronic address:

As one of the natural triterpenoids isolated from Anemone Raddeana Regel, Raddeanin A (RA) has been confirmed to possess therapeutic effects against multiple tumorigeneses, especially for the onset of glioblastoma and growth in human brains. However, the mechanism by which this happens remains poorly understood in terms of the vascular endothelium trafficking routine of RA through the brain-blood barrier (BBB). To seek such answers, human brain microenvironment endothelial cells (HBMECs) were used to stimulate the microenvironment in vitro, and to explore the intracellular accumulation of RA. Read More

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, a commonly consumed food, affects sirolimus level in a renal transplant recipient: a case report.

Ther Adv Drug Saf 2021 19;12:20420986211009358. Epub 2021 Apr 19.

Department of Nephrology, Hacettepe University Faculty of Medicine, Altindag, Ankara, Turkey.

Sirolimus is an immunosuppressive drug used to prevent graft rejection. Therapeutic drug monitoring is required as with other immunosuppressive drugs. Previous studies have shown the interactions between sirolimus and drugs that affect the activity of cytochrome P450 3A4 and P-glycoprotein. Read More

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Rapid Increase of Gastrointestinal P-Glycoprotein Functional Activity in Response to Etoposide Stimulation.

Biol Pharm Bull 2021 ;44(5):701-706

Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare.

We previously reported that exposure of human colon adenocarcinoma (Caco-2) cells to the bitter substance phenylthiocarbamide (PTC) rapidly enhanced the transport function of P-glycoprotein (P-gp). In this study, we investigated the short-term effect of etoposide, another bitter-tasting P-gp substrate, on P-gp transport function in the same cell line. We found that etoposide exposure significantly increased both the P-gp protein level in the plasma membrane fraction and the efflux rate of rhodamine123 (Rho123) in Caco-2 cells within 10 min. Read More

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January 2021

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System.

Int J Mol Sci 2021 Apr 18;22(8). Epub 2021 Apr 18.

Department of Pharmacognosy, Faculty of Pharmacy, Poznan University of Medical Sciences, Swiecickiego 4, 60-781 Poznań, Poland.

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and -glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood-brain barrier. Read More

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An Efficient Method for the Differentiation of Human iPSC-Derived Endoderm toward Enterocytes and Hepatocytes.

Cells 2021 Apr 6;10(4). Epub 2021 Apr 6.

Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.

The endoderm, differentiated from human induced pluripotent stem cells (iPSCs), can differentiate into the small intestine and liver, which are vital for drug absorption and metabolism. The development of human iPSC-derived enterocytes (HiEnts) and hepatocytes (HiHeps) has been reported. However, pharmacokinetic function-deficiency of these cells remains to be elucidated. Read More

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Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study.

Int J Mol Sci 2021 Apr 7;22(8). Epub 2021 Apr 7.

Department of Inorganic Chemistry, Wroclaw Medical University, Borowska 211A, Borowska 211A, 50-556 Wroclaw, Poland.

In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. Read More

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Changes in digoxin pharmacokinetics associated with hepatic P-glycoprotein upregulation in rats with non-alcoholic fatty liver disease.

Fundam Clin Pharmacol 2021 Apr 29. Epub 2021 Apr 29.

College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea.

Background & Objectives: Upregulation of hepatic P-glycoprotein (P-gp) expression has been reported in patients with non-alcoholic fatty liver disease (NAFLD) and rodent models thereof. Here, we explored the changes hepatic P-gp expression and activity in a NAFLD rat model and the effects thereof on the pharmacokinetics of digoxin (a probe substrate of P-gp).

Methods: Rats were fed a 1% (w/w) orotic acid-containing diet for 20 days to induce NAFLD; control rats received a normal diet. Read More

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Dietary bioactive diindolylmethane enhances the therapeutic efficacy of centchroman in breast cancer cells by regulating ABCB1/P-gp efflux transporter.

J Nutr Biochem 2021 Aug 25;94:108749. Epub 2021 Apr 25.

Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore 570020, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

Overexpression of drug efflux transporters is commonly associated with multidrug-resistance in cancer therapy. Here for the first time, we investigated the ability of diindolylmethane (DIM), a dietary bioactive rich in cruciferous vegetables, in enhancing the efficacy of Centchroman (CC) by modulating the drug efflux transporters in human breast cancer cells. CC is a selective estrogen receptor modulator, having promising therapeutic efficacy against breast cancer. Read More

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Effect of four ABCB1 genetic polymorphisms on the accumulation of darunavir in HEK293 recombinant cell lines.

Sci Rep 2021 Apr 26;11(1):9000. Epub 2021 Apr 26.

Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

The intracellular penetration of darunavir, a second-generation HIV protease inhibitor, is limited by the activity of the efflux P-glycoprotein (ABCB1). ABCB1 expression and/or activity levels can vary between individuals due to genetic polymorphisms including the c.1199G>A, c. Read More

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Transport of Alzheimer's associated amyloid-β catalyzed by P-glycoprotein.

PLoS One 2021 26;16(4):e0250371. Epub 2021 Apr 26.

Department of Biological Sciences, Southern Methodist University, Dallas, Texas, United States of America.

P-glycoprotein (P-gp) is a critical membrane transporter in the blood brain barrier (BBB) and is implicated in Alzheimer's disease (AD). However, previous studies on the ability of P-gp to directly transport the Alzheimer's associated amyloid-β (Aβ) protein have produced contradictory results. Here we use molecular dynamics (MD) simulations, transport substrate accumulation studies in cell culture, and biochemical activity assays to show that P-gp actively transports Aβ. Read More

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Influence of vitamin D treatment on functional expression of drug disposition pathways in human kidney proximal tubule cells during simulated uremia.

Xenobiotica 2021 Jun 18;51(6):657-667. Epub 2021 Apr 18.

Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.

Effects of cholecalciferol (VitD) and calcitriol (1,25-VitD), on the expression and function of major vitamin D metabolizing enzymes (cytochrome P450 [CYP]2R1, CYP24A1) and select drug transport pathways (P-gp, /OATP4C1) were evaluated in human kidney proximal tubule epithelial cells (hPTECs) under normal and uraemic serum conditions.hPTECs were incubated with 10% normal or uraemic serum for 24 h followed by treatment with 2% ethanol vehicle, or 100 and 240 nM doses of VitD, or 1,25-VitD for 6 days. The effects of treatment on mRNA and protein expression and functional activity of select CYP enzymes and transporters were assessedUnder uraemic serum, treatment with 1,25-VitD resulted in increased mRNA but decreased protein expression of CYP2R1. Read More

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Inhibition of P-Glycoprotein Does Not Increase the Efficacy of Proteasome Inhibitors in Multiple Myeloma Cells.

ACS Pharmacol Transl Sci 2021 Apr 4;4(2):713-729. Epub 2021 Feb 4.

College of Medicine and Public Health, Flinders University, Bedford Park, South Australia 5042, Australia.

P-Glycoprotein is a well-known drug transporter associated with chemotherapy resistance in a number of cancers, but its role in modulating proteasome inhibitor efficacy in multiple myeloma is not well understood. The second-generation proteasome inhibitor carfilzomib is thought to be a substrate of P-glycoprotein whose efficacy may correlate with P-glycoprotein activity; however, research concerning the first-in-class proteasome inhibitor bortezomib is inconsistent. We show that while P-glycoprotein gene expression increases with the disease stages leading to multiple myeloma it does not affect the survival of newly diagnosed patients treated with bortezomib. Read More

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Tetrahydroquinoline/4,5-Dihydroisoxazole Molecular Hybrids as Inhibitors of Breast Cancer Resistance Protein (BCRP/ABCG2).

ChemMedChem 2021 Apr 12. Epub 2021 Apr 12.

Faculty of Health Sciences, University of Eastern Finland, Kuopio, 70211, Finland.

Multidrug resistance (MDR) is one of the major factors in the failure of many chemotherapy approaches. In cancer cells, MDR is mainly associated with the expression of ABC transporters such as P-glycoprotein, MRP1 and ABCG2. Despite major efforts to develop new selective and potent inhibitors of ABC drug transporters, no ABCG2-specific inhibitors for clinical use are yet available. Read More

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