Anti-myeloma pro-apoptotic Pt(II) diiodido complexes

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dc.contributor.authorMasaryk, Lukášcs
dc.contributor.authorWeiser Drozdková, Denisacs
dc.contributor.authorSloczynska, Karolinacs
dc.contributor.authorMoncol, Jáncs
dc.contributor.authorMilde, Davidcs
dc.contributor.authorKrikavova, Radkacs
dc.contributor.authorPopiol, Justynacs
dc.contributor.authorPekala, Elzbietacs
dc.contributor.authorOndrušková, Katarínacs
dc.contributor.authorNemec, Ivancs
dc.contributor.authorSmešný, Kateřinacs
dc.contributor.authorŠtarha, Pavelcs
dc.coverage.issue11cs
dc.coverage.volume10cs
dc.date.issued2023-05-31cs
dc.description.abstractPlatinum-based agents unwaveringly hold their prominent position in cancer treatment. Current research emphasizes finding novel complexes for hard-to-treat cancers with minimum side effects, capable of overcoming resistance. This work presents easy-to-prepare diiodidoplatinum(II) complexes cis-[PtI2(L-n)(2)] (1-7) with imidazole derivatives (L-n), which were considerably effective against multiple myeloma cell lines U266B1 and KMS12-PE. The leading compound 6 (at 3 mu M concentration) extraordinarily reduced viability of U266B1 and KMS12-PE myeloma cells to 3.0% and 1.1%, respectively, and exceeded the conventional platinum-based anticancer drug cisplatin (93.1% and 88.3%, respectively) that is used clinically for the combination therapy of multiple myeloma. Complex 6 was significantly more effective in inducing apoptosis in KMS12-PE cells without interleukin-6 (IL-6) expression than in U266B1 cells with IL-6 expression. Complex 6 also induced apoptosis in co-culture of KMS12-PE with non-cancerous stromal fibroblasts (HS-5), and displayed markedly lower activity in the HS-5 stromal fibroblast cells than in myeloma cells, pointing out its pharmocologically prospective selectivity towards the cancer cells over the normal ones. No caspase 3/7 activity was detected in apoptotic KMS12-PE cells treated by complex 6 indicating a different mechanism of apoptosis action from cisplatin. This work demonstrates that simple non-classical platinum(II) complexes represent a new perspective for a monotherapy of hard-to-treat multiple myeloma.en
dc.formattextcs
dc.format.extent3307-3318cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationInorganic Chemistry Frontiers. 2023, vol. 10, issue 11, p. 3307-3318.en
dc.identifier.doi10.1039/d3qi00327bcs
dc.identifier.issn2052-1553cs
dc.identifier.orcid0000-0003-3231-7849cs
dc.identifier.other184251cs
dc.identifier.researcheridA-6969-2010cs
dc.identifier.scopus57201282084cs
dc.identifier.urihttp://hdl.handle.net/11012/244723
dc.language.isoencs
dc.publisherRoyal Society of Chemistrycs
dc.relation.ispartofInorganic Chemistry Frontierscs
dc.relation.urihttps://pubs.rsc.org/en/content/articlelanding/2023/QI/D3QI00327Bcs
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unportedcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/2052-1553/cs
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/cs
dc.subjectBONE-MARROW MICROENVIRONMENTen
dc.subjectVITRO ANTITUMOR-ACTIVITYen
dc.subjectDNA-BINDINGen
dc.subjectPLATINUM(II) COMPLEXESen
dc.subjectMULTIPLE-MYELOMAen
dc.subjectCYTOTOXIC ACTIVITIESen
dc.subjectANTICANCER ACTIVITYen
dc.subjectL-METHIONINEen
dc.subjectCELL-LINEen
dc.subjectCISPLATINen
dc.titleAnti-myeloma pro-apoptotic Pt(II) diiodido complexesen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-184251en
sync.item.dbtypeVAVen
sync.item.insts2025.02.03 15:50:53en
sync.item.modts2025.01.17 16:40:43en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Magneto-Optická a THz Spektroskopiecs
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