Insight into the toxic effects of cis-dichloridoplatinum(II) complexes containing 7-azaindole halogeno derivatives in tumor cells

0394814 - BFÚ 2014 RIV DE eng J - Článek v odborném periodiku
Muchová, T. - Prachařová, J. - Štarha, P. - Olivová, R. - Vrána, Oldřich - Benešová, B. - Kašpárková, J. - Trávníček, Z. - Brabec, Viktor
Insight into the toxic effects of cis-dichloridoplatinum(II) complexes containing 7-azaindole halogeno derivatives in tumor cells.
Journal of Biological Inorganic Chemistry. Roč. 18, č. 5 (2013), s. 579-589. ISSN 0949-8257. E-ISSN 1432-1327
Grant CEP: GA ČR(CZ) GAP301/10/0598; GA MŠMT(CZ) LH13096
Výzkumný záměr: CEZ:AV0Z50040702
Institucionální podpora: RVO:68081707
Klíčová slova: CELLULAR-RESPONSE * LUNG-CANCER * PLATINUM(II)
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 3.164, rok: 2013

The cisplatin analogues cis-[PtCl2(3ClHaza)(2)] (1) and cis-[PtCl2(3IHaza)(2)] (2) (3ClHaza and 3IHaza are 3-chloro-7-azaindole and 3-iodo-7-azaindole, respectively) are quite toxic to ovarian tumor cells, with moderately better IC50 values than for cisplatin in the cisplatin-sensitive cell line A2780. We investigated potential factors which might be involved in the mechanism underlying the cytotoxic effects of 1 and 2 and compared these factors with those involved in the mechanism underlying the effects of conventional cisplatin. Our data indicate that the higher cytotoxicity of 1 and 2 originates mainly from their efficient cellular accumulation, different effects at the level of cell cycle regulation, and reduced propensity for DNA adduct repair. Studies of their reactivity toward cellular components reveal efficient binding to DNA, which is typically required for an active platinum drug. Further results suggest that 1 and 2 are capable of circumventing resistance to cisplatin induced by alterations in cellular accumulation and DNA repair. Hence, the latter two factors appear to be responsible for differences in the toxicity of 1 or 2, and cisplatin in tumor cells.
Trvalý link: http://hdl.handle.net/11104/0222996