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dc.creatorJovanovic, Katarina K.
dc.creatorTanic, Miljana
dc.creatorIvanovic, Ivanka
dc.creatorGligorijević, Nevenka
dc.creatorDojčinović, Biljana
dc.creatorRadulovic, Sinisa
dc.date.accessioned2019-01-30T17:51:01Z
dc.date.available2019-01-30T17:51:01Z
dc.date.issued2016
dc.identifier.issn0162-0134
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1984
dc.description.abstractRuthenium(II)-arene complexes are promising drug candidates for the therapy of solid tumors. In previous work, seven new compounds of the general formula [Ru(eta(6)-p-cymene)(L1-7)Cl] were synthesized and characterized, of which the complex with L = isoquinoline-3-carboxylic acid (RuT7) was two times as active on HeLa cells compared to normal cell line MRC-5, as indicated by ICso values determined after 48 h of incubation (45.4 +/- 3.0 vs. 842 +/- 5.7 mu M, respectively). In the present study, cell cycle analysis of HeLa cells treated with RuT7 showed S phase arrest and an increase in sub-G1 population. The apoptotic potential of the title compound was confirmed with the Annexin V-FITC/PI assay together with a morphological evaluation of cells using fluorescent microscopy. Analysis of the intracellular accumulation of ruthenium showed 8.9 ng Ru/10(6) cells after 6 h of incubation. To gain further insight in the molecular mechanism of action of RuT7 on HeLa cells, a whole-transcriptome microarray gene expression analysis was performed. Analysis of functional categories and signaling and biochemical pathways associated with the response of HeLa cells to treatment with RuT7 showed that it leads the cells through the intrinsic (mitochondrial) apoptotic pathway, via indirect DNA damage due to the action of reactive oxygen species, and through direct DNA binding of RuT7. Statistical analysis for enrichment of gene sets associated with known drug-induced toxicities identified fewer associated toxicity profiles in RuT7-treated cells compared to cisplatin treatment. Altogether these results provide the basis for further development of RuT7 in animal and pre-clinical studies as a potential drug candidate.en
dc.publisherElsevier Science Inc, New York
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41026/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172017/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172030/RS//
dc.relation.isversionofhttps://cer.ihtm.bg.ac.rs/handle/123456789/4386
dc.rightsrestrictedAccess
dc.sourceJournal of Inorganic Biochemistry
dc.subjectRuthenium(II)en
dc.subjectAnticancer drugsen
dc.subjectApoptosisen
dc.subjectHeLaen
dc.subjectMicroarrayen
dc.titleCell cycle, apoptosis, cellular uptake and whole-transcriptome microarray gene expression analysis of HeLa cells treated with a ruthenium(II)-arene complex with an isoquinoline-3-carboxylic acid liganden
dc.typearticle
dc.rights.licenseARR
dcterms.abstractГлигоријевиц, Невенка; Ивановиц, Иванка; Јовановиц, Катарина К.; Таниц, Миљана; Радуловиц, Синиса; Дојчиновић, Биљана;
dc.citation.volume163
dc.citation.spage362
dc.citation.epage373
dc.citation.other163: 362-373
dc.citation.rankM22
dc.description.otherThe peer-reviewed version: [https://cer.ihtm.bg.ac.rs/handle/123456789/4386]
dc.identifier.pmid27118029
dc.identifier.doi10.1016/j.jinorgbio.2016.04.011
dc.identifier.rcubConv_3632
dc.identifier.scopus2-s2.0-84964297949
dc.identifier.wos000388546800039
dc.type.versionpublishedVersion


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