Phenoxodiol, a novel isoflavone derivative, inhibits dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague–Dawley rats

Abstract

The present study was undertaken to evaluate the potential cancer chemopreventive effects of novel synthetic derivatives of isoflavones. Initially these agents were tested in a mouse mammary organ culture (MMOC) model. Phenoxodiol (2H-1-benzopyran-7-O1,3-(4-hydroxyphenyl)), the most effective in this assay, was selected for further testing in female Sprague–Dawley rats. The agent was tested at 0 (basal diet), 50 and 75 mg/kg diet. Mammary carcinomas in these three groups were induced by dimethylbenz[a]anthracene (DMBA) injected 1 week after the animals started eating the experimental diets. Phenoxodiol significantly reduced tumour incidence rate at both doses (P⩽0.05). Tumour latency was increased from 70.4 days in the control group to 92.9 (P=0.04) days and 97.8 (P=0.03) days in the groups that were fed 50 and 75 mg/kg phenoxodiol, respectively. Compared with the control that was fed basal diet, tumour multiplicity was reduced by 42% (P=0.04) in the group that was fed 50 mg/kg phenoxodiol and by 49% (P=0.01) in the group that was fed 75 mg/kg phenoxodiol. Two additional groups that were not exposed to DMBA, one fed the basal diet and the other a diet containing 75 mg/kg phenoxodiol, were free of tumours. These data suggest that phenoxodiol is an effective chemopreventive agent against DMBA-induced mammary carcinogenesis.