The inverse association between a high
enterolactone (ENL) concentration in both urine and serum, and the risk of
breast cancer found in epidemiological studies suggests a chemopreventive action for ENL. However, no causal relationship has been established in clinical studies or in experimental models for
breast cancer. In the present study, the potential chemopreventive action of p.o. administered ENL (1 or 10 mg/kg of
body weight) was tested in 7,12-dimethylbenz(a)anthracene-induced
mammary cancers of the rat. Rats were maintained on a standard open-formula chow diet. Daily p.o. administration of ENL at a dose of 10 mg/kg of
body weight for 7 weeks significantly inhibited
tumor growth. The growth-inhibitory effect of ENL was more pronounced on the new
tumors, which developed during the treatment period, but ENL also inhibited the growth of those
tumors established before the start of the
lignan administration. The rat serum concentration of ENL, which illustrated a permanent positive effect on
breast cancer growth, was 0.4 microM, which is >10-fold as compared with the serum concentrations found in the general human population. The effect of ENL was not restricted to any specific histological
tumor type. ENL was demonstrated to act as a weak
aromatase inhibitor in vitro and to reduce the relative uterine weight of the 7,12-dimethylbenz(a)anthracene-treated nonovariectomized rats. However, in a short-term assay ENL had no effect on the uterine growth of the intact or
androstenedione-treated immature rats. Thus, the mechanism of the ENL action and its minimum or optimal daily dose remains to be clarified.