Key Findings:
High levels of the mammalian lignans derived from secoisolariciresinol diglucoside, SDG, enterodiol (ED) and enterolactone (EL) are associated with reduced breast cancer risk. In this study, the role of bacterial lignan transformation in breast cancer formation and selected cancer-associated parameters in a 7,12-dimethylbenz(a)anthracene (DMBA)-induced cancer model was assessed in germ-free rats and in rats colonized with lignan transforming bacteria (LCC). Bacteria of colonized the intestine of the LCC rats and enterolignans were produced from SDG in the LCC but not in the germ-free rats. Bacterial lignan transformation did not influence tumor incidence in the model but significantly lowered the number of tumors per tumor-bearing animal and the tumor size. The authors concluded from the Ki-67 index and the transferase-mediated nick end-labeling assay that the reduced tumor growth in LCC rats resulted from a lower proliferation and a higher apoptotic rate of the tumor cells. The authors concluded that the bacterial transformation of flaxseed-derived lignans is necessary for positive effects in a rat model of breast cancer.
ABSTRACT:
High dietary lignan exposure is implicated in a reduced breast cancer risk in women. The bacterial transformation of plant lignans to enterolignans is thought to be essential for this effect. To provide evidence for this assumption, gnotobiotic rats were colonized with the lignan-converting bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and Lactonifactor longoviformis (LCC rats). Germ-free rats were used as the control. All animals were fed a lignan-rich flaxseed diet and breast cancer was induced with 7,12-dimethylbenz(a)anthracene. The lignan secoisolariciresinol diglucoside was converted into the enterolignans enterodiol and enterolactone in the LCC but not in the germ-free rats. This transformation did not influence cancer incidence at the end of the 13 weeks experimental period but significantly decreased tumor numbers per tumor-bearing rat, tumor size, tumor cell proliferation and increased tumor cell apoptosis in LCC rats. No differences between LCC and control rats were observed in the expression of the genes encoding the estrogen receptors (ERs) a, ERb and G-coupled protein 30. The same was true for IGF-1 and EGFR involved in tumor growth. The activity of selected enzymes involved in the degradation of oxidants in plasma and liver was significantly increased in the LCC rats. However, plasma and liver concentrations of reduced glutathione and malondialdehyde, considered as oxidative stress markers, did not differ between the groups. In conclusion, our results show that the bacterial conversion of plant lignans to enterolignans beneficially influences their anticancer effects (Authors abstract).