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dc.creatorBjelogrlić, Snežana K.
dc.creatorTodorović, Tamara
dc.creatorCvijetić, Ilija
dc.creatorRodić, Marko V.
dc.creatorVujčić, Miroslava
dc.creatorMarković, Sanja
dc.creatorAraskov, Jovana
dc.creatorJanović, Barbara
dc.creatorEmhemmed, Fathi
dc.creatorMuller, Christian D.
dc.creatorFilipovic, Nenad R.
dc.date.accessioned2019-01-30T18:01:44Z
dc.date.available2019-01-30T18:01:44Z
dc.date.issued2019
dc.identifier.issn0162-0134
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/2493
dc.description.abstractA novel binuclear Cd complex (1) with hydrazone-based ligand was prepared and characterized by spectroscopy and single crystal X-ray diffraction techniques. Complex 1 reveals a strong pro-apoptotic activity in both human, mammary adenocarcinoma cells (MCF-7) and pancreatic AsPC-1 cancer stem cells (CSCs). While apoptosis undergoes mostly caspase-independent, 1 stimulates the activation of intrinsic pathway with noteworthy down regulation of caspase-8 activity in respect to non-treated controls. Distribution of cells over mitotic division indicates that 1 caused DNA damage in both cell lines, which is confirmed in DNA interaction studies. Compared to 1, cisplatin (CDDP) does not achieve cell death in 2D cultured AsPC-1 cells, while induces different pattern of cell cycle changes and caspase activation in 2D cultured MCF-7 cells, implying that these two compounds do not share similar mechanism of action. Additionally, 1 acts as a powerful inducer of mitochondrial superoxide production with dissipated trans-membrane potential in the majority of the treated cells already after 6 h of incubation. On 3D tumors, 1 displays a superior activity against CSC model, and at 100 M induces disintegration of spheroids within 2 days of incubation. Fluorescence spectroscopy, along with molecular docking show that compound 1 binds to the minor groove of DNA. Compound 1 binds to the human serum albumin (HSA) showing that the HSA can effectively transport and store 1 in the human body. Thus, our current study strongly supports further investigations on antitumor activity of 1 as a drug candidate for the treatment of highly resistant pancreatic cancer.en
dc.publisherElsevier Science Inc, New York
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172055/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Inorganic Biochemistry
dc.subjectCd(II) complexen
dc.subjectHydrazonesen
dc.subjectApoptosisen
dc.subjectCancer stem cellsen
dc.subjectDNA interactionsen
dc.subjectHSA interactionsen
dc.titleA novel binuclear hydrazone-based Cd(II) complex is a strong pro-apoptotic inducer with significant activity against 2D and 3D pancreatic cancer stem cellsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЦвијетић, Илија Н.; Вујчић, Мирослава; Јановић, Барбара; Бјелогрлић, Снежана К.; Филиповиц, Ненад Р.; Муллер, Цхристиан Д.; Родић, Марко В.; Марковић, Сања; Тодоровиц, Тамара Р.; Aрасков, Јована; Емхеммед, Фатхи;
dc.citation.volume190
dc.citation.spage45
dc.citation.epage66
dc.citation.other190: 45-66
dc.citation.rankM21~
dc.identifier.pmid30352315
dc.identifier.doi10.1016/j.jinorgbio.2018.10.002
dc.identifier.rcubConv_4035
dc.identifier.scopus2-s2.0-85055090720
dc.identifier.wos000452938900006
dc.type.versionpublishedVersion


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