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Potentiation of cytotoxic action of cis-[PtCl2(NH3)(1M7AI)] by UVA irradiation. Mechanistic insights
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SYSNO ASEP 0487346 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Potentiation of cytotoxic action of cis-[PtCl2(NH3)(1M7AI)] by UVA irradiation. Mechanistic insights Author(s) Prachařová, J. (CZ)
Intini, F. P. (IT)
Natile, G. (IT)
Kašpárková, Jana (BFU-R) RID, ORCID
Brabec, Viktor (BFU-R) RID, ORCIDNumber of authors 5 Source Title Inorganica chimica acta. - : Elsevier - ISSN 0020-1693
Roč. 472, MAR2018 (2018), s. 199-206Number of pages 8 s. Publication form Print - P Language eng - English Country NL - Netherlands Keywords cisplatin-dna adducts ; tumor-cells ; cross-links Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology Subject RIV - cooperation Inorganic Chemistry R&D Projects GA17-05302S GA ČR - Czech Science Foundation (CSF) LO1204 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BFU-R - RVO:68081707 UT WOS 000424293700020 DOI https://doi.org/10.1016/j.ica.2017.06.026 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2018
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