Different cell cycle modulation following treatment of human ovarian carcinoma cells with a new platinum(IV) complex vs cisplatin
Language English Country United States Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Amantadine analogs & derivatives pharmacology MeSH
- Cell Cycle drug effects MeSH
- Cisplatin pharmacology MeSH
- Carcinoma drug therapy metabolism MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Protein p53 metabolism MeSH
- Ovarian Neoplasms drug therapy metabolism MeSH
- Organoplatinum Compounds pharmacology MeSH
- Cell Proliferation drug effects MeSH
- bcl-2-Associated X Protein metabolism MeSH
- Cell Cycle Proteins metabolism MeSH
- Antineoplastic Agents pharmacology MeSH
- Proto-Oncogene Proteins c-mdm2 metabolism MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Amantadine MeSH
- bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) MeSH Browser
- Cisplatin MeSH
- MDM2 protein, human MeSH Browser
- Tumor Suppressor Protein p53 MeSH
- Organoplatinum Compounds MeSH
- bcl-2-Associated X Protein MeSH
- Cell Cycle Proteins MeSH
- Antineoplastic Agents MeSH
- Proto-Oncogene Proteins 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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