New insights into the molecular and epigenetic effects of antitumor Pt(IV)-valproic acid conjugates in human ovarian cancer cells

0446237 - BFÚ 2016 RIV US eng J - Článek v odborném periodiku
Novohradský, Vojtěch - Zerzánková, Lenka - Štěpánková, Jana - Vrána, Oldřich - Raveendran, R. - Gibson, D. - Kašpárková, Jana - Brabec, Viktor
New insights into the molecular and epigenetic effects of antitumor Pt(IV)-valproic acid conjugates in human ovarian cancer cells.
Biochemical Pharmacology. Roč. 95, č. 3 (2015), s. 133-144. ISSN 0006-2952. E-ISSN 1873-2968
Grant CEP: GA ČR(CZ) GA14-21053S; GA MŠMT(CZ) LD14019
Institucionální podpora: RVO:68081707
Klíčová slova: HISTONE DEACETYLASE INHIBITORS * MALIGNANT PLEURAL MESOTHELIOMA * VALPROIC ACID
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 5.091, rok: 2015

Substitutionally inert Pt(IV) prodrugs, combining bioactive axial ligands with Pt(IV) derivatives of antitumor Pt(II) compounds, represent a new generation of anticancer drugs. The rationale behind these prodrugs is to release, by reductive elimination inside the cancer cell, an active Pt(II) drug which binds nuclear DNA as well as bioactive ligands that may potentiate toxic effects of the Pt(II) drugs by an independent pathway. Platinum prodrugs, such as Pt(IV) derivatives of cisplatin containing axial valproic acid (VPA) ligands, destroy cancer cells with greater efficacy than conventional cisplatin. These axial ligands were chosen because VPA inhibits histone deacetylase (HDAC) activity, thereby decondensing chromatin and subsequently increasing the accessibility of DNA within chromatin to DNA-binding agents. We examined the mechanism of cytotoxic activity of Pt(IV) derivatives of cisplatin with VPA axial ligands. Particular attention was paid to the role of the VPA ligand in these Pt(IV) prodrugs in the mechanism underlying their toxic effects in human ovarian tumor cells.
Trvalý link: http://hdl.handle.net/11104/0248226