Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by novel acridine-based compounds
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25960253
DOI
10.1016/j.ejps.2015.04.023
PII: S0928-0987(15)00178-5
Knihovny.cz E-resources
- Keywords
- Acridine derivatives, DNA-binding, HL-60 cells, Topoisomerases I and II,
- MeSH
- Acridines chemical synthesis metabolism pharmacology MeSH
- Leukemia, Promyelocytic, Acute drug therapy enzymology pathology MeSH
- Time Factors MeSH
- Nucleic Acid Denaturation MeSH
- DNA Topoisomerases, Type I metabolism MeSH
- DNA Topoisomerases, Type II metabolism MeSH
- DNA chemistry metabolism MeSH
- Chemistry, Pharmaceutical MeSH
- Technology, Pharmaceutical methods MeSH
- Spectrometry, Fluorescence MeSH
- HL-60 Cells MeSH
- Topoisomerase I Inhibitors chemical synthesis metabolism pharmacology MeSH
- Topoisomerase II Inhibitors chemical synthesis metabolism pharmacology MeSH
- Nucleic Acid Conformation MeSH
- Cell Cycle Checkpoints drug effects MeSH
- Humans MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- Cell Proliferation drug effects MeSH
- Spectrophotometry, Ultraviolet MeSH
- Cell Survival drug effects MeSH
- Viscosity MeSH
- Hot Temperature MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acridines MeSH
- calf thymus DNA MeSH Browser
- DNA Topoisomerases, Type I MeSH
- DNA Topoisomerases, Type II MeSH
- DNA MeSH
- Topoisomerase I Inhibitors MeSH
- Topoisomerase II Inhibitors MeSH
- TOP1 protein, human MeSH Browser
HL-60 cancer cells were treated with a series of novel acridine derivatives (derivatives 1-4) in order to test the compounds' ability to inhibit both cancer cell growth and topoisomerase I and II activity. Binding studies of derivatives 1-4 with calf thymus DNA were also performed using a number of techniques (UV-Vis and fluorescence spectroscopy, thermal denaturation, linear dichroism and viscometry) to determine the nature of the interaction between the compounds and ctDNA. The binding constants for the complexes of the studied acridine derivatives with DNA were calculated from UV-Vis spectroscopic titrations (K=3.1×10(4)-2.0×10(3)M(-1)). Some of the compounds showed a strong inhibitory effect against Topo II at the relatively low concentration of 5μM. Topo I/II inhibition mode assays were also performed and verified that the novel compounds are topoisomerase suppressors rather than poisons. The biological activities of derivatives were studied using MTT assay and flow cytometric methods (detection of mitochondrial membrane potential, measurement of cell viability) after 24 and 48h incubation. The ability of derivatives to impair cell proliferation was tested by an analysis of cell cycle distribution.
References provided by Crossref.org
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