Search results for " Member 2"

showing 10 items of 39 documents

Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-fa…

2016

AbstractWe systematically characterised multifactorial multidrug resistance (MDR) in CEM/ADR5000 cells, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells developed in vitro. RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed. Chromosomal aberrations were identified by array-comparative genomic hybridisation (aCGH) and multicolour fluorescence in situ hybridisation (mFISH). Fifteen ATP-binding cassette transporters and numerous new genes were overexpressed in CEM/ADR5000 cells. The basic karyotype in CCRF-CEM cells consisted of 47, XX, der(5)t(5;14) (q35.33;q32.3), del(9) (p14.1), +20. CEM/ADR5000 cells acquired additional aber…

0301 basic medicineATP Binding Cassette Transporter Subfamily BDNA RepairDown-RegulationChromosomal translocationABCC5ArticleTranslocation GeneticTranscriptome03 medical and health sciences0302 clinical medicineATP Binding Cassette Transporter Subfamily G Member 2HumansGeneIn Situ Hybridization FluorescenceChromosome 7 (human)GeneticsComparative Genomic HybridizationGenomeLeukemiaMultidisciplinarybiologySequence Analysis RNAGene Expression ProfilingGenomicsNeoplasm ProteinsMultiple drug resistanceGene expression profiling030104 developmental biologyDrug Resistance Neoplasm030220 oncology & carcinogenesisbiology.proteinTranscriptomeComparative genomic hybridizationScientific Reports
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Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.

2018

Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1–3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4–10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6′-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the correspo…

0301 basic medicineATP Binding Cassette Transporter Subfamily BTumor suppressor geneCell SurvivalATP-binding cassette transporterNuphar03 medical and health sciences0302 clinical medicineAlkaloidsCell Line TumorNeoplasmsATP Binding Cassette Transporter Subfamily G Member 2HumansATP Binding Cassette Transporter Subfamily B Member 1Binding siteCytotoxicityGeneOncogeneChemistryPlant ExtractsABCB5General MedicineMolecular biologyAntineoplastic Agents PhytogenicNeoplasm ProteinsGene Expression Regulation NeoplasticMolecular Docking Simulation030104 developmental biologyCell cultureDrug Resistance Neoplasm030220 oncology & carcinogenesisSesquiterpenesFood ScienceFoodfunction
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Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes.

2016

Abstract Ethnopharmacological relevance Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs. Polyoxypregnanes (POPs) are identified as main constituents of this herb, and three of them have been re…

0301 basic medicineDrugAbcg2media_common.quotation_subjectAntineoplastic AgentsPharmacology03 medical and health sciences0302 clinical medicineCell Line TumorNeoplasmsDrug DiscoverymedicineATP Binding Cassette Transporter Subfamily G Member 2HumansATP Binding Cassette Transporter Subfamily B Member 1P-glycoproteinmedia_commonPharmacologybiologyChemistryPlant ExtractsCancerMarsdeniaTransportermedicine.diseaseFlow CytometryPregnanesDrug Resistance MultipleNeoplasm ProteinsMultiple drug resistanceGene Expression Regulation NeoplasticMolecular Docking Simulation030104 developmental biologyDrug Resistance Neoplasm030220 oncology & carcinogenesisCancer cellbiology.proteinEffluxMultidrug Resistance-Associated ProteinsJournal of ethnopharmacology
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Molecular partners of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, suggest its involvement in distinct cellular proces…

2018

This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1. We disclose the building of hNOT/ALG3 homodimers and provide experimental evidence f…

0301 basic medicineGlycosylationSaccharomyces cerevisiae ProteinsRNA-binding proteinSaccharomyces cerevisiaeBiologyEndoplasmic ReticulumMannosyltransferases03 medical and health scienceschemistry.chemical_compoundCongenital Disorders of GlycosylationNeoplasmsNuclear Receptor Subfamily 4 Group A Member 2GeneticsAnimalsDrosophila ProteinsHumansMolecular BiologyTranscription factorOSBPGeneGenetics (clinical)Cellular compartmentEndoplasmic reticulumMembrane ProteinsRNA-Binding ProteinsGeneral MedicineLRP1Cell biology030104 developmental biologychemistryNerve DegenerationDrosophilaCarrier ProteinsHuman molecular genetics
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Sequential cleavage of the proteins encoded by HNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, results in products acting…

2017

This study provides first insights into the biosynthesis, structure, biochemistry and complex processing of the proteins encoded by hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID (NOT) and the yeast asparagine linked glycosylation 3 gene (ALG3), which encodes a mannosyltransferase. Unambiguous evidence that both the fly and human proteins act as mannosyltransferases has not been provided yet. Previously, we showed that hNOT/ALG3 encodes two alternatively spliced main transcripts, hNOT-1/ALG3-1 and hNOT-4/ALG3-4, and their 15 truncated derivatives that lack diverse sets of exons and/or carry point mutations that result in premature termination codons. Here we show that t…

0301 basic medicineMannosyltransferaseGlycosylationSaccharomyces cerevisiae ProteinsGlycosylationProtein ConformationRNA SplicingSaccharomyces cerevisiaeBiologyMannosyltransferases03 medical and health scienceschemistry.chemical_compoundExonNuclear Receptor Subfamily 4 Group A Member 2GeneticsAnimalsHumansAmino Acid SequenceAsparagineMolecular BiologyGeneGenetics (clinical)Cellular compartmentPoint mutationComputational BiologyMembrane ProteinsExonsGeneral MedicineCell biologyAlternative Splicing030104 developmental biologychemistryCodon NonsenseDrosophilaCytokinesisHuman Molecular Genetics
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Cytotoxic activity of medicinal plants of the Kakamega County (Kenya) against drug-sensitive and multidrug-resistant cancer cells

2018

Abstract Ethnopharmacological relevance The geographical location of Kakamega County proximal to the Kakamega Rain Forest in Kenya and its rich flora represents an interesting resource of traditional medicinal plants. The medicinal plants in the present study are traditionally used to treat cancer in Kakamega County as recorded in published literature. Aim of the study Due to multidrug resistance (MDR) and severe side effects of currently used drugs in clinical oncology, new candidate compounds are urgently required to improve treatment outcome. The present study explored the in vitro cytotoxic potential of 34 organic and 19 aqueous extracts of Kakamega medicinal plants towards sensitive an…

0301 basic medicinePhyllanthusCell SurvivalDrug resistancePharmacognosyInhibitory Concentration 5003 medical and health sciences0302 clinical medicineCell Line TumorOxazinesDrug DiscoveryHarunganaATP Binding Cassette Transporter Subfamily G Member 2HumansATP Binding Cassette Transporter Subfamily B Member 1Medicinal plantsMedicine African TraditionalPharmacologyPrunus africanaPlants MedicinalbiologyTraditional medicineBridelia micranthabiology.organism_classificationAntineoplastic Agents PhytogenicNeoplasm ProteinsErbB ReceptorsGene Expression Regulation NeoplasticMultiple drug resistance030104 developmental biologyXanthenesDrug Resistance Neoplasm030220 oncology & carcinogenesisDrug Therapy CombinationJournal of Ethnopharmacology
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Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

2021

Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima (M. tenacissima) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells v…

ABCC1 ATP binding cassette subfamily C member 1IC50 half maximal inhibitory concentrationMultidrug resistancePharmacologyNADPH reduced nicotinamide adenine dinucleotide phosphateF bioavailabilitychemistry.chemical_compoundPCR polymerase chain reaction0302 clinical medicineMDR multidrug resistanceECL electrochemiluminescencet1/2 elimination half-lifeLC–MS liquid chromatography coupled with mass spectrometryN.D. not detectedGeneral Pharmacology Toxicology and PharmaceuticsBBB blood–brain barriermedia_commonATF3 activating transcription factor 30303 health sciencesChemistryABC ATP-binding cassetteNMPA National Medical Products AdministrationPXR pregnane X receptorSDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresisHBSS Hankʹs balanced salt solutionABCB1Combination chemotherapyProdrugMarsdenia tenacissimaCmax peak concentrationPaclitaxelGAPDH glyceraldehyde-3-phosphate dehydrogenase030220 oncology & carcinogenesisBHI brain heart infusionOriginal ArticleAUC0–∞ area under plasma concentration vs. time curveMRT mean residence timeDrugmedia_common.quotation_subjectRM1-950Vd volume of distributionABCB1 ATP binding cassette subfamily B member 1UIC-2 mouse monoclonal ABCB1 antibodyABCG2 ATP binding cassette subfamily G member 2Combination chemotherapyCYP cytochrome P450 isozymePI propidium iodideTEER transepithelial electrical resistance03 medical and health sciencesPBS phosphate buffer salineFBS fetal bovine serumDox doxorubicinIn vivoPOP polyoxypregnanemedicine030304 developmental biologyEVOM epithelial tissue voltohmmeterTmax time for peak concentrationCancerLBE lowest binding energyPE phycoerythrinmedicine.diseaseMultiple drug resistancePolyoxypregnanePapp apparent permeabilityN.A. not applicableCancer cellH&E hematoxylin and eosinMDR1a multidrug resistance protein 1aTherapeutics. PharmacologyqPCR quantitative PCRM. tenacissima Marsdenia tenacissimaCL clearanceSD standard derivationActa Pharmaceutica Sinica B
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Putative molecular determinants mediating sensitivity or resistance towards carnosic acid tumor cell responses.

2020

Abstract Background Carnosic acid (CA) is one of the main constituents in rosemary extract. It possesses valuable pharmacological properties, including anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer activities. Numerous in vitro and in vivo studies investigated the anticancer profile of CA and emphasized its potentiality for cancer treatment. Nevertheless, the role of multidrug-resistance (MDR) related mechanisms for CA's anticancer effect is not yet known. Purpose We investigated the cytotoxicity of CA against known mechanisms of anticancer drug resistance (P-gp, ABCB5, BCRP, EGFR and p53) and determined novel putative molecular factors associated with cellular response to…

ATP Binding Cassette Transporter Subfamily BPharmaceutical ScienceBiologyFlow cytometry03 medical and health sciences0302 clinical medicineWestern blotCell Line TumorDrug DiscoverymedicineATP Binding Cassette Transporter Subfamily G Member 2HumansATP Binding Cassette Transporter Subfamily B Member 1Cytotoxicity030304 developmental biologyPharmacology0303 health sciencesmedicine.diagnostic_testABCB5Antineoplastic Agents PhytogenicDrug Resistance MultipleNeoplasm ProteinsBlotErbB ReceptorsComplementary and alternative medicineApoptosisDrug Resistance NeoplasmPharmacogenetics030220 oncology & carcinogenesisCancer cellAbietanesCancer researchMolecular MedicineSignal transductionTumor Suppressor Protein p53Phytomedicine : international journal of phytotherapy and phytopharmacology
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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…

ATP Binding Cassette Transporter Subfamily BReserpineAngiogenesisPharmaceutical SciencePharmacologyBiologyRauwolfiaGene Knockout TechniquesCell Line TumorDrug DiscoverymedicineATP Binding Cassette Transporter Subfamily G Member 2HumansCytotoxicityPharmacologyWnt signaling pathwayReserpineAntineoplastic Agents PhytogenicDrug Resistance MultipleNeoplasm ProteinsErbB ReceptorsMolecular Docking SimulationComplementary and alternative medicineCell cultureApoptosisDoxorubicinDrug Resistance NeoplasmCancer cellMolecular MedicineATP-Binding Cassette TransportersErlotinibTumor Suppressor Protein p53medicine.drugPhytomedicine : international journal of phytotherapy and phytopharmacology
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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…

Abcg2Drug ResistancePharmaceutical ScienceATP-binding cassette transporterMicroarraySubfamily Gchemistry.chemical_compoundGene Knockout Techniques0302 clinical medicineEpidermal growth factorPhytogenicDrug DiscoveryATP Binding Cassette Transporter Subfamily G Member 2Cancer0303 health sciencesTumorLeukemiabiologyChemistryABCB5TransfectionCell cycleNeoplasm ProteinsGene Expression Regulation NeoplasticErbB ReceptorsMolecular Docking SimulationSubfamily B030220 oncology & carcinogenesisMolecular MedicineCitrullus colocynthiMember 2Member 1ATP Binding Cassette Transporter Subfamily BATP Binding Cassette TransporterAntineoplastic AgentsCell Line03 medical and health sciencesCell Line TumorHumansATP Binding Cassette Transporter Subfamily B Member 1030304 developmental biologyCucurbitacin EPharmacologyNeoplasticTraditional herbal medicineCancer; Citrullus colocynthis; Drug resistance; Microarray; Traditional herbal medicine; ATP Binding Cassette Transporter Subfamily B; ATP Binding Cassette Transporter Subfamily B Member 1; ATP Binding Cassette Transporter Subfamily G Member 2; Antineoplastic Agents Phytogenic; Cell Line Tumor; Citrullus colocynthis; Doxorubicin; Drug Resistance Neoplasm; ErbB Receptors; Gene Expression Regulation Neoplastic; Gene Knockout Techniques; Humans; Leukemia; Molecular Docking Simulation; Neoplasm Proteins; Triterpenes; Tumor Suppressor Protein p53Antineoplastic Agents PhytogenicTriterpenesComplementary and alternative medicineGene Expression RegulationDrug Resistance NeoplasmDoxorubicinCancer cellbiology.proteinCancer researchNeoplasmCitrullus colocynthisTumor Suppressor Protein p53
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