Transplatin is cytotoxic when photoactivated: enhanced formation of DNA cross-links
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17181161
DOI
10.1021/jm0606692
Knihovny.cz E-resources
- MeSH
- Cisplatin pharmacology MeSH
- DNA Footprinting MeSH
- DNA drug effects metabolism radiation effects MeSH
- Keratinocytes drug effects radiation effects MeSH
- Comet Assay MeSH
- Cells, Cultured drug effects radiation effects MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy MeSH
- Ovarian Neoplasms drug therapy pathology radiotherapy MeSH
- DNA Damage drug effects radiation effects MeSH
- Proteins metabolism MeSH
- Antineoplastic Agents pharmacology MeSH
- Cross-Linking Reagents pharmacology MeSH
- Stereoisomerism MeSH
- Ultraviolet Rays * MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cisplatin MeSH
- DNA MeSH
- Proteins MeSH
- Antineoplastic Agents MeSH
- Cross-Linking Reagents MeSH
- transplatin MeSH Browser
It is well-known that although cisplatin, [cis-[PtCl2(NH3)2], is an anticancer drug, its isomer transplatin is not cytotoxic. Here we show that transplatin is almost as cytotoxic as cisplatin when treated cells (human keratinocytes HaCaT and ovarian cancer A2780 cells) are irradiated with UVA light (50 min, 1.77 mW cm-2). Chemical studies show that light activates both chloride ligands of transplatin, and experiments on pSP73 plasmid DNA and a 23 base-pair DNA duplex show that irradiation can greatly enhance formation of interstrand cross-links and of DNA-protein cross-links (which are not formed in the dark). Comet assays showed that UVA irradiation of transplatin-treated cells resulted in an increased inhibition of H2O2-induced DNA migration, supporting the conclusion that the cytotoxicity of photoactivated transplatin is mainly due to formation of DNA interstrand and DNA-protein cross-links.
References provided by Crossref.org
Excited-State Cis and Trans Pt(IV) Diamine Anticancer Complexes
Antitumor carboplatin is more toxic in tumor cells when photoactivated: enhanced DNA binding
