Issue 11, 2023

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


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(Ln)2] (1–7) with imidazole derivatives (Ln), which were considerably effective against multiple myeloma cell lines U266B1 and KMS12-PE. The leading compound 6 (at 3 μM 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.

Graphical abstract: Anti-myeloma pro-apoptotic Pt(ii) diiodido complexes

Supplementary files

Article information

Article type
Research Article
20 Feb 2023
01 May 2023
First published
03 May 2023
This article is Open Access
Creative Commons BY-NC license

Inorg. Chem. Front., 2023,10, 3307-3318

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

L. Masaryk, D. Weiser Drozdková, K. Słoczyńska, J. Moncol’, D. Milde, R. Křikavová, J. Popiół, E. Pękala, K. Ondrušková, I. Nemec, K. Smešný Trtková and P. Štarha, Inorg. Chem. Front., 2023, 10, 3307 DOI: 10.1039/D3QI00327B

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