Platinum (IV) derivative with adamantylamine-LA-12-represents a new generation of highly efficient anti-cancer drug derived from cisplatin and is currently in the final stage of phase I clinical trials. Understanding the specific mechanisms of its effects on cell cycle is necessary for defining the mode of action of LA-12. In this study, we characterized the ability of LA-12 to induce cell cycle perturbations in ovarian cancer cell line A2780 as compared to equitoxic cisplatin treatment. LA-12 induced a permanent accumulation of A2780 cells in S phase while cisplatin caused G2/M arrest at 24-h time point, where we also detected an increased expression of Gadd45alpha protein. Although both derivatives induced a rapid increase of p53 expression, this was not associated with a down-regulation of Mdm2 protein. Increased expression of p21(Cip1/WAF1) protein and its association with cyclins A and B1 suggested that this cyclin-dependent kinase inhibitor might contribute significantly to the observed perturbations of cell cycle. The results of this study provide insight into the mechanism of action of platinum-based derivative with adamantylamine on cell cycle in ovarian cancer cells. The differences between effects of LA-12 and cisplatin suggest that more attention should be paid to elucidation of modes of action of novel platinum(IV) complexes at cellular level.

• MeSH
• amantadin analogy a deriváty   farmakologie   MeSH
• buněčný cyklus účinky léků   MeSH
• cisplatina farmakologie   MeSH
• karcinom farmakoterapie   metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory vaječníků farmakoterapie   metabolismus   MeSH
• organoplatinové sloučeniny farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• protein X asociovaný s bcl-2 metabolismus   MeSH
• proteiny buněčného cyklu metabolismus   MeSH
• protinádorové látky farmakologie   MeSH
• protoonkogenní proteiny c-mdm2 metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• amantadin MeSH
• bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) MeSH Prohlížeč
• cisplatina MeSH
• MDM2 protein, human MeSH Prohlížeč
• nádorový supresorový protein p53 MeSH
• organoplatinové sloučeniny MeSH
• protein X asociovaný s bcl-2 MeSH
• proteiny buněčného cyklu MeSH
• protinádorové látky MeSH
• protoonkogenní proteiny c-mdm2 MeSH