Potentiation of mitochondrial dysfunction in tumor cells by conjugates of metabolic modulator dichloroacetate with a Pt(IV) derivative of oxaliplatin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00506413" target="_blank" >RIV/68081707:_____/16:00506413 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/16:33161184

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0162013415301331?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0162013415301331?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jinorgbio.2015.12.003" target="_blank" >10.1016/j.jinorgbio.2015.12.003</a>

Result language

angličtina

Original language name

Potentiation of mitochondrial dysfunction in tumor cells by conjugates of metabolic modulator dichloroacetate with a Pt(IV) derivative of oxaliplatin

Original language description

The molecular and cellular mechanisms of enhanced toxic effects in tumor cells of the Pt(IV) derivatives of antitumor oxaliplatin containing axial dichloroacetate (DCA) ligands were investigated. DCA ligands were chosen because DCA has shown great potential as an apoptosis sensitizer and anticancer agent reverting the Wartburg effect. In addition, DCA reverses mitochondrial changes in a wide range of cancers, promoting tumor cell apoptosis in a mitochondrial-dependent pathway. We demonstrate that (i) the transformation of oxaliplatin to its Pt(IV) derivatives containing axial DCA ligands markedly enhances toxicity in cancer cells and helps overcome inherent and acquired resistance to cisplatin and oxaliplatin, (ii) a significant fraction of the intact molecules of DCA conjugates with Pt(IV) derivative of oxaliplatin accumulates in cancer cells where it releases free DCA, (iii) mechanism of biological action of the Pt(IV) derivatives of oxaliplatin containing DCA ligands is connected with the effects of DCA released in cancer cells from the Pt(IV) prodrugs on mitochondria and metabolism of glucose, (iv) treatments with the Pt(IV) derivatives of oxaliplatin containing DCA ligands activate an autophagic response in human colorectal cancer cells, (v) the toxic effects in cancer cells of the Pt(IV) derivatives of oxaliplatin containing DCA ligands can be potentiated if cells are treated with these prodrugs in combination with 5-fluorouracil. These properties of the Pt(IV) derivatives of oxaliplatin containing DCA ligands provide opportunities for further development of new platinum-based agents with the capability of killing cancer cells resistant to conventional antitumor platinum drugs used in the clinic. (C) 2015 Elsevier Inc. All rights reserved.

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

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA14-21053S" target="_blank" >GA14-21053S: Mechanistic studies on dual targeting of DNA and histone deacetylase with bifunctional inhibitors</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

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

Name of the periodical

Journal of Inorganic Biochemistry

ISSN

0162-0134

e-ISSN

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Volume of the periodical

156

Issue of the periodical within the volume

MAR 2016

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

89-97

UT code for WoS article

000370769400010

EID of the result in the Scopus database

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