Publication detail

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

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.

Original Title

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

Type

journal article in Web of Science

Language

English

Original 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.

Keywords

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

Authors

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.

Released

31. 5. 2023

Publisher

Royal Society of Chemistry

Location

CAMBRIDGE

ISBN

2052-1553

Periodical

Inorganic Chemistry Frontiers

Year of study

10

Number

11

State

United Kingdom of Great Britain and Northern Ireland

Pages from

3307

Pages to

3318

Pages count

12

URL

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

Full text in the Digital Library

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

BibTex

@article{BUT184251,
  author="Lukáš {Masaryk} and Denisa {Weiser Drozdková} and Karolina {Sloczynska} and Ján {Moncol} and David {Milde} and Radka {Krikavova} and Justyna {Popiol} and Elzbieta {Pekala} and Katarína {Ondrušková} and Ivan {Nemec} and Kateřina {Smešný} and Pavel {Štarha}",
  title="Anti-myeloma pro-apoptotic Pt(II) diiodido complexes",
  journal="Inorganic Chemistry Frontiers",
  year="2023",
  volume="10",
  number="11",
  pages="3307--3318",
  doi="10.1039/d3qi00327b",
  issn="2052-1553",
  url="https://pubs.rsc.org/en/content/articlelanding/2023/QI/D3QI00327B"
}