Whole flaxseed diet alters estrogen metabolism to promote 2-methoxtestradiol-induced apoptosis in hen ovarian cancer

The study reported here demonstrates that a flaxseed-supplemented diet causes ovarian tumors in the laying hen to undergo apoptosis, resulting in a reduction of tumor burden, reducing the frequency and severity of ovarian cancer. We have previously shown in normal ovaries that flaxseed and its components down-regulate ERalpha and alter the expression of enzymes that metabolize estrogen. In this study, we analyzed the effects of the two main components of whole flaxseed, ligan and omega 3 fatty acids on estrogen metabolism and the estrogen receptor in ovarian tumors. ER alpha expression was up-regulated in the ovarian tumors and was not affected by diet. Liver CYP1A1 expression was significantly increased by the whole flaxseed diet with a corresponding increase in 2-methoxyestradiol plasma levels. We also observed increased p38 and ERK 1/2 MAPK activation in the ovary as well as an increase in apoptosis in the tumor epithelium. SMAD 7, a factor involved in the 2-methoxyestradiol-mediated apoptosis pathway was also up-regulated in tumors from the whole flaxseed diet group. 2-methoxyestradiol-induced antitumor effects were further validated by in human ovarian cancer cells. This study details the effect of flaxseed diet on estrogen metabolism and demonstrates the antiovarian cancer effects of 2-methoxyestradiol.