Show simple item record

dc.creatorPodolski-Renić, Ana
dc.creatorJadranin, Milka
dc.creatorStanković, Tijana
dc.creatorBanković, Jasna
dc.creatorStojkovic, Sonja
dc.creatorChiourea, Maria
dc.creatorAljančić, Ivana S.
dc.creatorVajs, Vlatka
dc.creatorTešević, Vele
dc.creatorRuzdijic, Sabera
dc.creatorGagos, Sarantis
dc.creatorTanić, Nikola
dc.creatorPešić, Milica
dc.date.accessioned2018-11-22T00:23:50Z
dc.date.available2018-11-22T00:23:50Z
dc.date.issued2013
dc.identifier.issn0344-5704
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/1393
dc.description.abstractMulti-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.en
dc.publisherSpringer, New York
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41031/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172053/RS//
dc.relationCancer and Control of Genomic Integrity (CANGENIN) COST Action [BM0703]
dc.rightsrestrictedAccess
dc.sourceCancer Chemotherapy and Pharmacology
dc.subjectMulti-drug resistanceen
dc.subjectCytogeneticsen
dc.subjectLoss of heterozygosityen
dc.subjectP-glycoproteinen
dc.subjectAnticancer agentsen
dc.titleMolecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testingen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractБанковиц, Јасна; Јадранин, Милка; Стојковиц, Соња; Тешевић, Веле; Песиц, Милица; Подолски-Рениц, Aна; Гагос, Сарантис; Вајс, Влатка; Цхиоуреа, Мариа; Таниц, Никола; Aљанциц, Ивана С.; Руздијиц, Сабера; Станковиц, Тијана;
dc.citation.volume72
dc.citation.issue3
dc.citation.spage683
dc.citation.epage697
dc.identifier.wos000323653600020
dc.identifier.doi10.1007/s00280-013-2247-1
dc.citation.other72(3): 683-697
dc.citation.rankM22
dc.identifier.pmid23934261
dc.type.versionpublishedVersionen
dc.identifier.scopus2-s2.0-84883488322
dc.identifier.rcubKon_2513


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record