Number of the records: 1

Different affinity of nuclear factor-kappa B proteins to DNA modified by antitumor cisplatin and its clinically ineffective trans isomer

SYSNO ASEP	0435173
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Different affinity of nuclear factor-kappa B proteins to DNA modified by antitumor cisplatin and its clinically ineffective trans isomer
Author(s)	Kašpárková, Jana (BFU-R)_{RID, ORCID} Thibault, T. (FR) Kostrhunová, Hana (BFU-R)_{RID, ORCID} Štěpánková, Jana (BFU-R) Vojtíšková, Marie (BFU-R) Muchová, T. (CZ) Midoux, P. (FR) Malinge, J.M. (FR) Brabec, Viktor (BFU-R)_{RID, ORCID}
Number of authors	9
Source Title	FEBS Journal - ISSN 1742-464X Roč. 281, č. 5 (2014), s. 1393-1408
Number of pages	16 s.
Publication form	Print - P
Language	eng - English
Country	GB - United Kingdom
Keywords	antitumor activity ; cisplatin ; DNA
Subject RIV	BO - Biophysics
R&D Projects	GAP301/10/0598 GA ČR - Czech Science Foundation (CSF)
Institutional support	BFU-R - RVO:68081707
UT WOS	000332083600006
DOI	10.1111/febs.12711
Annotation	Nuclear factor-kappa B (NF-kB) comprises a family of protein transcription factors that have a regulatory function in numerous cellular processes and are implicated in the cancer cell response to antineoplastic drugs, including cisplatin. We characterized the effects of DNA adducts of cisplatin and ineffective transplatin on the affinity of NF-kB proteins to their consensus DNA sequence (kB site). Although the kB site-NF-B protein interaction was significantly perturbed by DNA adducts of cisplatin, transplatin adducts were markedly less effective both in cell-free media and in cellulo using a decoy strategy derivatized-approach. Moreover, NF-B inhibitor JSH-23 [4-methyl-N-1-(3-phenylpropyl)benzene-1,2-diamine] augmented cisplatin cytotoxicity in ovarian cancer cells and the data showed strong synergy with JSH-23 for cisplatin. The distinctive structural features of DNA adducts of the two platinum complexes suggest a unique role for conformational distortions induced in DNA by the adducts of cisplatin with respect to inhibition of the binding of NF-kB to the platinated kB sites.
Workplace	Institute of Biophysics
Contact	Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244
Year of Publishing	2015

Number of the records: 1