In vitro cytotoxic potential and mechanism of action of selected coumarins, using human renal cell lines.
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.
Finn
Gregory J
GJ
Department of Applied Science, National Centre for Sensor Research, School of Science, Institute of Technology, Tallaght, Dublin 24, Ireland.
Kenealy
Emma
E
Creaven
Bernadette S
BS
Egan
Denise A
DA
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
D003374:Coumarins; D003603:Cytotoxins