A potential method to improve the in vitro cytotoxicity of half-sandwich Os(II) complexes against A2780 cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F18%3A73591077" target="_blank" >RIV/61989592:15310/18:73591077 - isvavai.cz</a>
Result on the web
<a href="https://pubs.rsc.org/en/content/articlepdf/2018/dt/c8dt00193f" target="_blank" >https://pubs.rsc.org/en/content/articlepdf/2018/dt/c8dt00193f</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/c8dt00193f" target="_blank" >10.1039/c8dt00193f</a>
Alternative languages
Result language
angličtina
Original language name
A potential method to improve the in vitro cytotoxicity of half-sandwich Os(II) complexes against A2780 cells
Original language description
The [Os((6)-pcym)(dpa)(VP)]PF6 (1-VP) complex contains the histone deacetylase (HDAC) inhibitor valproate (2-propylpentanoate; VP) as a monodentate O-donor ligand and shows ca. 3-fold higher in vitro cytotoxicity against A2780 human ovarian carcinoma cells than its chlorido analogue [Os((6)-pcym)(dpa)Cl]PF6 (1-Cl); pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), dpa = 2,2-dipyridylamine. The complex 1-VP showed promising selectivity towards the A2780 ovarian carcinoma cell line (IC50 = 20.9 M) over normal human hepatocytes (IC50 > 200.0 M). Moreover, the complex 1-VP was found to be inactive against MCF-7 (breast adenocarcinoma), PANC-1 (pancreatic adenocarcinoma) and HT-29 (colon carcinoma) up to a concentration of 100 M. Detailed flow cytometry studies indicated that treatment of A2780 cells with complex 1-VP led to induction of apoptosis, production of reactive oxygen species (ROS) and superoxide (SO) anion radicals, as well as mitochondrial membrane potential depletion and cell cycle perturbations. The microscopic assessment (standard hematoxylin/eosin staining) revealed signs of morphological changes associated with the progression of apoptosis in A2780 cells treated with the IC50 concentration of the complex 1-VP. Consistent with the intracellular production of ROS and SO, the complex 1-VP induced hydroxyl radical formation, as proved by EPR spin trapping experiments. This case study suggests that replacement of the chlorido ligand of half-sandwich Os(ii) complexes by a releasable monodentate biologically active ligand (e.g., VP used in this study) is an effective strategy for the development of novel non-platinum cytotoxic agents.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10402 - Inorganic and nuclear chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
DALTON TRANSACTIONS
ISSN
1477-9226
e-ISSN
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Volume of the periodical
47
Issue of the periodical within the volume
16
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
5714-5724
UT code for WoS article
000430802500027
EID of the result in the Scopus database
2-s2.0-85045958670