Platinum(IV) complex with adamantylamine overcomes intrinsic resistance to cisplatin in ovarian cancer cells
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16364413
DOI
10.1016/j.ygyno.2005.11.016
PII: S0090-8258(05)01006-1
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma drug therapy metabolism pathology MeSH
- Amantadine administration & dosage analogs & derivatives MeSH
- Cell Cycle drug effects MeSH
- Cell Growth Processes drug effects MeSH
- Drug Resistance, Neoplasm MeSH
- Cisplatin administration & dosage MeSH
- DNA, Neoplasm biosynthesis MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neoplasm Proteins biosynthesis MeSH
- Ovarian Neoplasms drug therapy metabolism pathology MeSH
- Organoplatinum Compounds administration & dosage pharmacology MeSH
- Poly(ADP-ribose) Polymerases metabolism MeSH
- Antineoplastic Combined Chemotherapy Protocols pharmacology MeSH
- Vault Ribonucleoprotein Particles biosynthesis MeSH
- Blotting, Western MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amantadine MeSH
- bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) MeSH Browser
- Cisplatin MeSH
- DNA, Neoplasm MeSH
- major vault protein MeSH Browser
- Neoplasm Proteins MeSH
- Organoplatinum Compounds MeSH
- Poly(ADP-ribose) Polymerases MeSH
- Vault Ribonucleoprotein Particles MeSH
OBJECTIVES: The resistance of tumor cells to cisplatin remains a major cause of treatment failure in cancer patients. In this study, the ability of Pt(IV) complex with adamantylamine-LA-12 and its reduced counterpart with lower oxidation state Pt(II)-LA-9 to overcome intrinsic cisplatin resistance was investigated. METHODS: The ovarian adenocarcinoma SK-OV-3 cells were exposed to cisplatin, LA-9, or LA-12 for 72 h and the effects of drug concentrations that caused 10% or 50% inhibition of cell proliferation were determined. After 24-72 h of sustained exposure viability, apoptosis and inhibition of proliferation were analyzed. DNA synthesis and cell cycle analysis were performed simultaneously in order to determine the modulation of cell cycle after platinum complexes treatment. RESULTS: Lung Resistance-related Protein (LRP/MVP) was detected in SK-OV-3 cells but not in the other two ovarian cancer lines with different sensitivity to cisplatin. LRP/MVP overexpression may be an important factor contributing to intrinsic cisplatin resistance. Interestingly, Pt(IV) complex-LA-12 had approximately 2.7-fold lower IC(50) concentration than LA-9 or cisplatin in SK-OV-3 cells. Moreover, LA-12 caused persistent accumulation of cells in S-phase of the cell cycle while LA-9 and cisplatin treatment-induced S-phase arrest was transient and shifted to G(2)/M-phase at later intervals. Apoptosis seemed to be not the dominant type of cell death caused by such the derivatives, but it was the most intensive after LA-12 treatment. CONCLUSIONS: We found strong differences between effects of Pt(IV) complex-LA-12 and Pt(II) derivatives-LA-9 and cisplatin on cytokinetic parameters. Overall, LA-12 but not its reduced Pt(II) counterpart LA-9 is the compound effective in p53 null human ovarian cancer cells and it is able to overcome intrinsic cisplatin resistance in these cells.
References provided by Crossref.org
The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo
