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dc.creatorLeskovac, Andreja
dc.creatorPetrović, Sandra
dc.creatorLazarevic-Pasti, Tamara
dc.creatorKrstić, Milena
dc.creatorVasić, Vesna
dc.date.accessioned2020-06-03T14:28:43Z
dc.date.available2020-06-03T14:28:43Z
dc.date.issued2018
dc.identifier.issn0949-8257
dc.identifier.urihttp://vet-erinar.vet.bg.ac.rs/handle/123456789/1672
dc.description.abstractIn recent years, the search for effective anticancer compounds based on transition metal complexes has been the focus of medical investigations. The synergy between the ruthenium(II) and N-alkylphenothiazine counter-ions (chlorpromazine hydrochloride, thioridazine hydrochloride and trifluoperazine dihydrochloride, respectively) through the formation of three different complexes (1-3) was investigated. We explored whether the selected counter-ions and complexes might affect redox homeostasis and genome integrity of normal human blood cells, and induce an inhibition of Na+/K+-ATPase and AChE at pharmacologically relevant doses. Our results have shown that counter-ions and complexes did not affect the activity of Na+/K+-ATPase, while AChE activity was inhibited in a dose-dependent manner. All investigated compounds disturbed the viability and redox homeostasis of lymphocytes. Complexes 1 and 2 displayed potent cytotoxic and prooxidant action while complex 3 behaved as a weaker genotoxic inducer. Still, the tested complexes appeared to be less genotoxic and more cytostatic than the corresponding counter-ions. The effects of selected complexes were also tested in PC12 and U2OS cancer cells with special attention being given to the ability of phenothiazines to affect dopamine D2 receptors. Using the confocal laser scanning microscopy, we observed that all the complexes reduced cell viability. Although all investigated complexes have been bound to the dopamine receptor D-2-eGFP, only complex 3 reduced its surface density and increased its lateral mobility in investigated cell lines. Albeit the role of alternative targets for complex 3 cannot be ruled out, its effects should be further examined as potential treatment strategy against cancer cells that overexpress D2.en
dc.publisherSpringer, New York
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172023/RS//
dc.relationCOST actionEuropean Cooperation in Science and Technology (COST) [MP1302]
dc.rightsrestrictedAccess
dc.sourceJournal of Biological Inorganic Chemistry
dc.subjectRuthenium (II)-N-alkyl phenothiazine complexesen
dc.subjectCytotoxicityen
dc.subjectOxidative stressen
dc.subjectDopamine D2 receptoren
dc.titleRuthenium(II)-N-alkyl phenothiazine complexes as potential anticancer agentsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЛесковац, Aндреја; Васић, Весна; Крстић, Милена; Петровић, Сандра; Лазаревиц-Пасти, Тамара;
dc.citation.volume23
dc.citation.issue5
dc.citation.spage689
dc.citation.epage704
dc.citation.other23(5): 689-704
dc.citation.rankM21
dc.identifier.wos000435951600001
dc.identifier.doi10.1007/s00775-018-1560-x
dc.identifier.pmid29644470
dc.identifier.scopus2-s2.0-85049351568
dc.identifier.rcubconv_2387
dc.type.versionpublishedVersion


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