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-NO2-7-OHC) and 7,8-dihydroxycoumarin (7,8-OHC). 6-NO2-7-OHC induced cytoloxicity 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-NO2-7-OHC and 7,8-OHC might have a therapeutic role to play in the treatment of renal cell carcinoma. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.