Anti-myeloma pro-apoptotic Pt(II) diiodido complexes
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Date
2023-05-31
Authors
Masaryk, Lukáš
Weiser Drozdková, Denisa
Sloczynska, Karolina
Moncol, Ján
Milde, David
Krikavova, Radka
Popiol, Justyna
Pekala, Elzbieta
Ondrušková, Katarína
Nemec, Ivan
ORCID
0000-0003-3231-7849Advisor
Referee
Mark
Journal Title
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Volume Title
Publisher
Royal Society of Chemistry
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Abstract
Platinum-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.
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Citation
Inorganic Chemistry Frontiers. 2023, vol. 10, issue 11, p. 3307-3318.
https://pubs.rsc.org/en/content/articlelanding/2023/QI/D3QI00327B
https://pubs.rsc.org/en/content/articlelanding/2023/QI/D3QI00327B
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Peer-reviewed
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Published version
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en
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Defence
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Creative Commons Attribution-NonCommercial 3.0 Unported
http://creativecommons.org/licenses/by-nc/3.0/
http://creativecommons.org/licenses/by-nc/3.0/