Potentiation of cytotoxic action of cis-[PtCl2(NH3)(1M7AI)] by UVA irradiation. Mechanistic insights

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F18%3A00487346" target="_blank" >RIV/68081707:_____/18:00487346 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/18:73589825

Result on the web

<a href="http://dx.doi.org/10.1016/j.ica.2017.06.026" target="_blank" >http://dx.doi.org/10.1016/j.ica.2017.06.026</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ica.2017.06.026" target="_blank" >10.1016/j.ica.2017.06.026</a>

Result language

angličtina

Original language name

Potentiation of cytotoxic action of cis-[PtCl2(NH3)(1M7AI)] by UVA irradiation. Mechanistic insights

Original language description

The design of photosensitive platinum antitumor drugs has been shown to be a very promising approach to enhance the low selectivity of antitumor platinum drugs towards cancer tissues. Here, we show that UVA irradiation can substantially potentiate the toxicity of a cisplatin derivative, cis-[PtCl2(NH3) (1-methyl-7-azaindole)], in tumor cells. We used methods of molecular biophysics and cellular biology to investigate the mechanism underlying this effect. We find that the enhanced phototoxicity of cis[PtCl2(NH3)(1-methyl-7-azaindole)] is connected with the capability of this complex to cleave DNA strands. We demonstrate that production of reactive singlet oxygen, conditioned by the presence of the 1-methyl-7-azaindole ligand, is responsible for the cleavage of DNA strands not only in vitro but also in living cells. Our findings also reveal that UVA irradiation of DNA modified by cis-[PtCl2(NH3)(1-methyl-7-azaindole)] may result in a significant increase in the number of more toxic interstrand cross-links in DNA. Collectively, these data provide convincing evidence that the replacement of the ammine in the molecule of cisplatin by the 1-methyl-7-azaindole ligand might lead to a new potential candidate for photoactivated chemotherapy (PACT) against some types of cancer. (C) 2017 Elsevier B.V. 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

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

2018

Confidentiality

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

Name of the periodical

Inorganica chimica acta

ISSN

0020-1693

e-ISSN

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Volume of the periodical

472

Issue of the periodical within the volume

MAR2018

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

8

Pages from-to

199-206

UT code for WoS article

000424293700020

EID of the result in the Scopus database

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