Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
31673793
DOI
10.1007/s00775-019-01735-5
PII: 10.1007/s00775-019-01735-5
Knihovny.cz E-zdroje
- Klíčová slova
- Antitumor activity, Ex vivo, In vivo, Platinum(II) complexes, Seliciclib derivatives,
- MeSH
- apoptóza účinky léků MeSH
- cisplatina škodlivé účinky MeSH
- lidé MeSH
- lymfom patologie MeSH
- myši inbrední DBA MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- organoplatinové sloučeniny chemie MeSH
- oxaláty chemie MeSH
- protinádorové látky chemie farmakologie MeSH
- roskovitin chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cisplatina MeSH
- organoplatinové sloučeniny MeSH
- oxaláty MeSH
- protinádorové látky MeSH
- roskovitin MeSH
This work presents a deeper pharmacological evaluation of two formerly prepared and characterized, and highly in vitro cytotoxic platinum(II) oxalato complexes [Pt(ox)(L1)2] (1) and [Pt(ox)(L2)2] (2), containing the derivatives of cyclin-dependent kinase inhibitor (CDKi) seliciclib ((R)-roscovitine, CYC202) coordinating as N-donor carrier ligands, i.e., 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L1) and 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L2). The positive results of in vitro cytotoxicity screening on human cancer cell lines (HeLa, HOS, A2780, A2780R, G361 and MCF7 with IC50 at low micromolar levels) published previously, motivated us to perform extended preclinical in vitro experiments to reveal the mechanisms associated with the induction of cancer cell death. In addition, the in vivo antitumor activity was evaluated using the mouse lymphocytic leukaemia L1210 model. The obtained results revealed that complex 1 exceeds the antitumor effect of cisplatin (as for the extension of life-span of mice) and shows far less adverse effects as compared to reference drug cisplatin. The in vitro and ex vivo studies of cellular effects and molecular mechanisms of cell death induction showed that the mechanism of action of complex 1 is essentially different from that of cisplatin. The obtained results showed a possible way how to obtain antitumor active platinum(II) oxalato complexes with better therapeutic profile than contemporary used platinum-based therapeutics.
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