title: In vitro cytotoxic potential and mechanism of action of selected coumarins, using human renal cell lines.
abstract: This study determined the selective cytotoxicity of eight coumarin compounds to human renal carcinoma cells, relative to non-carcinoma proximal tubular cells. Selectivity cytotoxicity was observed following exposure to 6-nitro-7-hydroxycoumarin (6-NO(2)-7-OHC) and 7,8-dihydroxycoumarin (7,8-OHC). 6-NO(2)-7-OHC induced cytotoxicity was irreversible in both cell lines, unlike 7,8-OHC, which was reversible in the carcinoma cells only. Mobility shift and BrdU incorporation assays showed that both compounds did not intercalate DNA but had a concentration-dependent inhibitory effect on its synthesis. All coumarins studied were found to be non-mutagenic using the standard Ames test. These results would suggest that 6-NO(2)-7-OHC and 7,8-OHC might have a therapeutic role to play in the treatment of renal cell carcinoma.
authors.affiliation: Department of Applied Science, National Centre for Sensor Research, School of Science, Institute of Technology, Tallaght, Dublin 24, Ireland.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Finn
authors.forename: Emma
authors.initials: E
authors.lastname: Kenealy
authors.forename: Bernadette S
authors.initials: BS
authors.lastname: Creaven
authors.forename: Denise A
authors.initials: DA
authors.lastname: Egan
mesh_terms: D000230:Adenocarcinoma; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003374:Coumarins / Q000633:toxicity*; D003603:Cytotoxins / Q000633:toxicity*; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007668:Kidney; D007680:Kidney Neoplasms; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D003374:Coumarins; D003603:Cytotoxins