Suppression of 7,12-dimethylbenz(a) anthracene-induced mammary tumorigenesis by glyceollins

Scope: Our previous study showed that glyceollins induced phase 2 detoxifying and antioxidant enzymes. As chemical carcinogens can be detoxified by metabolic activity of phase 2 enzymes, subsequently decreasing their tumorigenic potential, we investigated whether 7,12dimethylbenz(a) anthracene (DMBA)-inducedmammary tumorigenesis could be attenuated by treatment with glyceollins in a mouse model. Methods and results: Pretreatment with glyceollins (5 mg/kg body weight) caused a significant reduction in tumor formation and an increase in survival rate. The protective effect of glyceollins against DMBA-induced tumorigenesis was found to be mainly associated with their potential to induce phase 2/antioxidant enzymes that are, in turn, regulated by the nuclear factor E2-related factor 2 signaling pathway, and to a less extent to suppress phase 1 enzymes. As glyceollins increased the number of terminal end buds, a tumor-prone mammary tissue type in mice, it is unlikely that they exert their antitumorigenic action through their estrogenic activity. Conclusion: Glyceollins were found to have a protective effect in a chemically induced mammary tumor model.