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Synthesis of a monofunctional platinum compound and its activity alone and in combination with phytochemicals in ovarian tumor models.
- Source :
-
Anticancer research [Anticancer Res] 2014 Dec; Vol. 34 (12), pp. 7077-90. - Publication Year :
- 2014
-
Abstract
- Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. In this study, a new monofunctional planaramineplatinum(II) complex, namely tris(8-hydroxyquinoline)monochloroplatinum(II) chloride (coded as LH3), was synthesised and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistant A2780 (A2780(ZD0473R)) cancer cell lines, alone and in combination with the phytochemicals curcumin, genistein and resveratrol. Cellular levels of glutathione in A2780 and A2780(cisR) cell lines before and after treatment with LH3 and its combinations with genistein and curcumin were also determined. Interaction of the compounds with salmon sperm DNA, pBR322 plasmid DNA and damage to DNA in A2780 and A2780(cisR) cells due to interaction with LH3-alone and in combination with phytochemicals were also investigated. LH3 was found to be much more active than cisplatin against the resistant tumor models and greatest synergism in activity was observed when combinations of LH3 with genistein and curcumin were administered as a bolus. For combinations of LH3 with the phytochemicals, platinum accumulation and the level of Pt-DNA binding were found to be greater in the resistant A2780(cisR) cell line than in the parental A2780 cell line. Greater activity of LH3 than cisplatin against the resistant ovarian cell lines indicates that it may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy.<br /> (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Subjects :
- Cell Line, Tumor
Cell Survival drug effects
Cisplatin pharmacology
Curcumin pharmacology
DNA drug effects
DNA Fragmentation drug effects
Deoxyribonuclease BamHI metabolism
Drug Evaluation, Preclinical
Drug Resistance, Neoplasm
Drug Synergism
Female
Genistein pharmacology
Glutathione analysis
Humans
Organoplatinum Compounds chemical synthesis
Ovarian Neoplasms pathology
Plasmids drug effects
Plasmids genetics
Platinum Compounds chemical synthesis
Resveratrol
Stilbenes pharmacology
Antineoplastic Agents pharmacology
Antineoplastic Combined Chemotherapy Protocols pharmacology
Organoplatinum Compounds pharmacology
Ovarian Neoplasms drug therapy
Phytochemicals pharmacology
Platinum Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-7530
- Volume :
- 34
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 25503135