Different cell cycle modulation following treatment of human ovarian carcinoma cells with a new platinum(IV) complex vs cisplatin
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
- 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
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.
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