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

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

Článek WoS

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.

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.

BONE-MARROW MICROENVIRONMENT; VITRO ANTITUMOR-ACTIVITY; DNA-BINDING; PLATINUM(II) COMPLEXES; MULTIPLE-MYELOMA; CYTOTOXIC ACTIVITIES; ANTICANCER ACTIVITY; L-METHIONINE; CELL-LINE; CISPLATIN

BONE-MARROW MICROENVIRONMENT; VITRO ANTITUMOR-ACTIVITY; DNA-BINDING; PLATINUM(II) COMPLEXES; MULTIPLE-MYELOMA; CYTOTOXIC ACTIVITIES; ANTICANCER ACTIVITY; L-METHIONINE; CELL-LINE; CISPLATIN

MASARYK, L.; WEISER DROZDKOVÁ, D.; SLOCZYNSKA, K.; MONCOL, J.; MILDE, D.; KRIKAVOVA, R.; POPIOL, J.; PEKALA, E.; ONDRUŠKOVÁ, K.; NEMEC, I.; SMEŠNÝ, K.; ŠTARHA, P.

2024

31.05.2023

Royal Society of Chemistry

CAMBRIDGE

2052-1553

Inorganic Chemistry Frontiers

10

11

Čínská lidová republika

3307

3318

12

https://pubs.rsc.org/en/content/articlelanding/2023/QI/D3QI00327B

http://hdl.handle.net/11012/244723

d3qi00327b