Antitumour activity of coumarin and 7-hydroxycoumarin against 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinomas

Abstract

Female SD rats with established 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumours were treated with coumarin (20 mg/kg body weight; six times per week) or its metabolite 7-hydroxycoumarin (20 mg/kg) for 4 weeks. The anti-oestrogen tamoxifen (8.8 mg/kg) served as the reference drug. The inhibitory effect of coumarin was similar to that of tamoxifen [mean change of tumour area: 428% (coumarin) compared to 528% (tamoxifen); control 822%]. The strongest inhibition was observed with 7-hydroxycoumarin (248%); the difference compared to the control was significant (P < 0.01). Neither coumarin nor 7-hydroxycoumarin reduced the number of tumours appearing during treatment as tamoxifen did. However, the size of the tumours treated with coumarin or its metabolite was generally much smaller than those in the tamoxifen group or in the control group. From the data obtained it appears that coumarin and 7-hydroxycoumarin inhibit the growth of tumours that have reached a certain size but do not prevent the formation of tumours after exposure to the carcinogen.