Cytotoxicity, mutagenicity, cellular uptake, DNA and glutathione interactions of lipophilic trans-platinum complexes tethered to 1-adamantylamine
| Autor: | Jana Kasparkova, Dan Gibson, Viktor Brabec, Francesco P. Intini, Pavla Heringova, Alina Nemirovski, Giovanni Natile, Anna Halámiková |
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| Rok vydání: | 2008 |
| Předmět: |
Hypoxanthine Phosphoribosyltransferase
Organoplatinum Compounds Stereochemistry chemistry.chemical_element Antineoplastic Agents Biochemistry Inorganic Chemistry DNA Adducts chemistry.chemical_compound Cell Line Tumor Amantadine medicine Humans Cytotoxic T cell Cytotoxicity Cisplatin Antitumor activity Chemistry Circular Dichroism DNA Glutathione Growth inhibition Platinum Mutagens medicine.drug |
| Zdroj: | Journal of Inorganic Biochemistry. 102:1077-1089 |
| ISSN: | 0162-0134 |
| DOI: | 10.1016/j.jinorgbio.2007.12.015 |
| Popis: | Cytotoxicity and mutagenicity of trans,trans,trans-[PtCl2(CH3COO)2(NH3)(1-adamantylamine)] [trans-adamplatin(IV)] and its reduced analog trans-[PtCl2(NH3)(1-adamantylamine)] [trans-adamplatin(II)] were examined. In addition, the several factors underlying biological effects of these trans-platinum compounds using various biochemical methods were investigated. A notable feature of the growth inhibition studies was the remarkable circumvention of both acquired and intrinsic cisplatin resistance by the two lipophilic trans-compounds. Interestingly, trans-adamplatin(IV) was considerably less mutagenic than cisplatin. Consistent with the lipophilic character of trans-adamplatin complexes, their total accumulation in A2780 cells was considerably greater than that of cisplatin. The results also demonstrate that trans-adamplatin(II) exhibits DNA binding mode markedly different from that of ineffective transplatin. In addition, the reduced deactivation of trans-adamplatin(II) by glutathione seems to be an important determinant of the cytotoxic effects of the complexes tested in the present work. The factors associated with cytotoxic and mutagenic effects of trans-adamplatin complexes in tumor cell lines examined in the present work are likely to play a significant role in the overall antitumor activity of these complexes. |
| Databáze: | OpenAIRE |
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