Introduction: Coumarins are a large group of natural compounds, which are mainly found in the families Rutaceae and Apiaceae. In the last decade it has been shown that prenyloxycoumarins, as secondary metabolites, have valuable biological activities. For instance, 7-isopentenyloxycoumarin, a type of prenyloxycoumarins, has shown promising anti-cancer, anti-inflammatory, anti-fungal and anti-microbial effects. This compound can be either extracted from plants or chemically synthesised and this property makes it an interesting compound for further investigations. Here we report the DNA-damaging effects of 7-isopentenyloxycoumarin on TCC cells in vitro. Methods: 7-isopentenyloxycoumarin was synthesised by reaction between isopentenyl bromide and hydroxycoumarin at room temperature in the presence of acetone and was then purified by column chromatography. TCC cells (as cancerous cells) and HDF cells (as normal cells) were grown and treated with 10 to 100 μg/ml concentrations of this compound. Equivalent percentages of dimethylsulfoxide (DMSO) were used as controls. Cell viability was measured 24, 48 and 72 hours after treatments by MTT assay. The DNA-damaging activity of 7-isopentenyloxycoumarin was quantified using comet assay. Untreated cells and cells treated with DMSO were used as controls. Each cell was analysed with \\\"TriTek Cometscore version 1.5\\\" software and the DNA damage was reported as percent tail DNA. Results: Results showed that 7-isopentenyloxycoumarin reached its IC50 at concentration of 65 μg/ml after 72 hours on TCC cells. On the other hand, it did not have any cytotoxic effect on HDF cells. Investigating the DNA-damaging effect of this compound on TCC cells showed that 65 μg/ml 7-isopentenyloxycoumarin can induce DNA lesion by 32.68%, significantly (P< 0.001) higher than DMSO control, and no significant difference was observed among cells treated with DMSO and untreated cells. Conclusion: The results indicated that 7-isopentenyloxycoumarin had cytotoxic effects on TCC cells. Exploring the mechanism of this action on cancerous cells by comet assay revealed that 7-isopentenyloxycoumarin can induce DNA lesion. Therefore, 7-isopentenyloxycoumarin might be considered as an anti-tumour agent. More investigations are required to confirm the reproducibility and mechanism of these observations in other cell lines.

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