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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/61989592:15310/18:73589825

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Inorganica chimica acta

ISSN

0020-1693

e-ISSN

—

Svazek periodika

472

Číslo periodika v rámci svazku

MAR2018

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

199-206

Kód UT WoS článku

000424293700020

EID výsledku v databázi Scopus

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