2007
Horváth, Viktor; Soucek, Karel; Svihálková-Sindlerová, Lenka; Vondrácek, Jan; Blanárová, Olga; Hofmanová, Jirina; Sova, Petr; Kozubík, Alois
Different cell cycle modulation following treatment of human ovarian carcinoma cells with a new platinum(IV) complex vs cisplatin. Journal Article
In: Investigational new drugs, vol. 25, no. 5, pp. 435–443, 2007, ISSN: 0167-6997, (Place: United States).
Abstract | Links | BibTeX | Tags: Amantadine/*analogs & derivatives/pharmacology, Antineoplastic Agents/*pharmacology, bcl-2-Associated X Protein/metabolism, Carcinoma/drug therapy/metabolism, Cell Cycle Proteins/metabolism, Cell Cycle/*drug effects, Cell Line, Cell Proliferation/drug effects, Cisplatin/*pharmacology, Female, Humans, Organoplatinum Compounds/*pharmacology, Ovarian Neoplasms/drug therapy/metabolism, Proto-Oncogene Proteins c-mdm2/metabolism, Tumor, Tumor Suppressor Protein p53/metabolism
@article{horvath_different_2007,
title = {Different cell cycle modulation following treatment of human ovarian carcinoma cells with a new platinum(IV) complex vs cisplatin.},
author = {Viktor Horváth and Karel Soucek and Lenka Svihálková-Sindlerová and Jan Vondrácek and Olga Blanárová and Jirina Hofmanová and Petr Sova and Alois Kozubík},
doi = {10.1007/s10637-007-9062-7},
issn = {0167-6997},
year = {2007},
date = {2007-10-01},
journal = {Investigational new drugs},
volume = {25},
number = {5},
pages = {435–443},
abstract = {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.},
note = {Place: United States},
keywords = {Amantadine/*analogs & derivatives/pharmacology, Antineoplastic Agents/*pharmacology, bcl-2-Associated X Protein/metabolism, Carcinoma/drug therapy/metabolism, Cell Cycle Proteins/metabolism, Cell Cycle/*drug effects, Cell Line, Cell Proliferation/drug effects, Cisplatin/*pharmacology, Female, Humans, Organoplatinum Compounds/*pharmacology, Ovarian Neoplasms/drug therapy/metabolism, Proto-Oncogene Proteins c-mdm2/metabolism, Tumor, Tumor Suppressor Protein p53/metabolism},
pubstate = {published},
tppubtype = {article}
}
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.