Enterolactone inhibits the growth of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in the rat

• Published in: Molecular cancer therapeutics 2002-08, Vol.1 (10), p.869
• Main Authors: Saarinen, Niina M, Huovinen, Riikka, Wärri, Anni, Mäkelä, Sari I, Valentín-Blasini, Liza, Sjöholm, Rainer, Ammälä, Jenni, Lehtilä, Reko, Eckerman, Christer, Collan, Yrjö U, Santti, Risto S
• Format: Article
• Language: English
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - blood; 4-Butyrolactone - pharmacokinetics; 4-Butyrolactone - urine; 9,10-Dimethyl-1,2-benzanthracene - pharmacology; Animals; Aromatase Inhibitors; Carcinogens; Cell Division - drug effects; Enzyme Inhibitors - pharmacology; Estrogens - pharmacology; Estrogens, Non-Steroidal - blood; Estrogens, Non-Steroidal - urine; Female; Isoflavones; Lignans - blood; Lignans - metabolism; Lignans - pharmacokinetics; Lignans - urine; Mammary Neoplasms, Animal - drug therapy; Medicin och hälsovetenskap; Models, Chemical; Organ Size; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Time Factors; Uterus - drug effects
• ISSN: 1535-7163

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.