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

0435173 - BFÚ 2015 RIV GB eng J - Článek v odborném periodiku
Kašpárková, Jana - Thibault, T. - Kostrhunová, Hana - Štěpánková, Jana - Vojtíšková, Marie - Muchová, T. - Midoux, P. - Malinge, J.M. - Brabec, Viktor
Different affinity of nuclear factor-kappa B proteins to DNA modified by antitumor cisplatin and its clinically ineffective trans isomer.
FEBS Journal. Roč. 281, č. 5 (2014), s. 1393-1408. ISSN 1742-464X. E-ISSN 1742-4658
Grant CEP: GA ČR(CZ) GAP301/10/0598
Institucionální podpora: RVO:68081707
Klíčová slova: antitumor activity * cisplatin * DNA
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 4.001, rok: 2014

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.
Trvalý link: http://hdl.handle.net/11104/0239098