Epigenetic and antitumor effects of platinum (IV)-octanoato conjugates

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00485646" target="_blank" >RIV/68081707:_____/17:00485646 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/17:73583761

Result on the web

<a href="http://dx.doi.org/10.1038/s41598-017-03864-w" target="_blank" >http://dx.doi.org/10.1038/s41598-017-03864-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-017-03864-w" target="_blank" >10.1038/s41598-017-03864-w</a>

Result language

angličtina

Original language name

Epigenetic and antitumor effects of platinum (IV)-octanoato conjugates

Original language description

We present the anticancer properties of cis, cis, trans-[Pt(IV)(NH3)(2)Cl-2(OA)(2)] [Pt(IV)diOA] (OA = octanoato), Pt(IV) derivative of cisplatin containing two OA units appended to the axial positions of a six-coordinate Pt(IV) center. Our results demonstrate that Pt(IV) diOA is a potent cytotoxic agent against many cancer cell lines (the IC50 values are approximately two orders of magnitude lower than those of clinically used cisplatin or Pt(IV) derivatives with biologically inactive axial ligands). Importantly, Pt(IV) diOA overcomes resistance to cisplatin, is significantly more potent than its branched Pt(IV) valproato isomer and exhibits promising in vivo antitumor activity. The potency of Pt(IV) diOA is a consequence of several factors including enhanced cellular accumulation correlating with enhanced DNA platination and cytotoxicity. Pt(IV) diOA induces DNA hypermethylation and reduces mitochondrial membrane potential in cancer cells at levels markedly lower than the IC50 value of free OA suggesting the synergistic action of platinum and OA moieties. Collectively, the remarkable antitumor effects of Pt(IV) diOA are a consequence of the enhanced cellular uptake which makes it possible to simultaneously accumulate high levels of both cisplatin and OA in cells. The simultaneous dual action of cisplatin and OA by different mechanisms in tumor cells may result in a markedly enhanced and unique antitumor effects of Pt(IV) prodrugs.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

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)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

JUN2017

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

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UT code for WoS article

000403413700113

EID of the result in the Scopus database

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