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.
Department of Physiology, Southern Illinois School of Medicine, Carbondale, IL, 62901, USA.
Anushka
A
Dikshit
Department of Physiology, Southern Illinois School of Medicine, Carbondale, IL, 62901, USA.
Karen
K
Hales
Department of Physiology, Southern Illinois School of Medicine, Carbondale, IL, 62901, USA. Electronic address: dhales@siumed.edu.
Dale Buchanan
DB
Hales
D000077584:2-Methoxyestradiol; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002645:Chickens; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D019587:Dietary Supplements; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D019597:Flax; D006801:Humans; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D010053:Ovary / Q000378:metabolism*; D051906:Smad7 Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047628:Estrogen Receptor alpha; D051906:Smad7 Protein; D004958:Estradiol; D000077584:2-Methoxyestradiol; D065633:Cytochrome P-450 CYP1B1; D051544:Cytochrome P-450 CYP3A; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
2-Methoxtestradiol; Apoptosis; Estrogen metabolism; Flaxseed; Ovarian cancer