Ovarian cancer is the most lethal of the gynecological malignacies and the 5th leading cause of cance death in women. The etiology of ovarian cancer is poorly understood and there are no suitable early detection markers. Due to the late stage at which the disease is usually diagnosed the survival rate is very low and conventional treatment modalities or intervention strategies are usually ineffective. A diet which is high in meats and low in vegetables may be corellated with increased ovarian cancer incidence. An imbalance of omega 3 (OM-3FA) and omega 6 (OM-6FA) fatty acids contributes to excess cancer risk. Studies indicate that populations that consume high amounts of OM-3FA have lower incidences of breast, prostate and colon cancers than do those that consume less OM-3FA. Thus increasing the consumption of OM-3FA may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. Flaxseed is an excellent source of dietary fiber, the OM-3FA alpha-linolenic acid (ALA), and phytoestrogen lignans, which are potent anti-estrogens that have been shown to have anti-proliferative and pro-apoptotic activities in certain cancers. An effective treatment or dietary intervention that significantly reduces the progression of ovarian cancer has the potential for turning ovarian cancer into a disease that women die WITH not from. The proposed studies will test the effectiveness of a flaxseed-enriched diet in the suppression of ovarian cancer, and examine the mechanism of action of omega-3 fatty acids and enteroestrogens using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that a flaxseed enriched diet will cause a significant reduction in the severity of ovarian carcinoma in the laying hen. Furthermore, we hypothesize that dietary intervention with flaxseed results in amelioration of ovarian cancer severity due to the synergistic action of omega-3 fatty acids and phytoestrogen lignans. Identification of molecular targets whose expression is affected by flax enriched diet will provide insight into the etiology of ovarian cancer and will provide the foundation for developing functional food based dietary intervention for the prevention and treatment of ovarian cancer in women.
Three Specific Aims are proposed based on the innovative used of three test diets: regular flaxseed vs. high lignan/low omega-3 fatty acid containing flaxseed (Linola) vs. flaxseed oil-derived omega-3 (high omega-3/low lignan).
Aim 1) to determine the optimum dose of flaxseed;
Aim 2) to evaluate the mechanism through which flaxseed reduces the severity of ovarian cancer diets containing either high lignan (Linola) or high omega-3(flaxseed oil) will b compared to regular flaxseed;
and Aim 3) to evaluate the efficacy of one-year dietary intervention with these diet's on the severity of ovarian cancer in old laying hens.
Research into ovarian cancer, a highly lethal disease, has been limited by the lack of suitable animal models, because, with the exception of the laying hen, no other animals are inflicted with the same type of ovarian cancer that affects women. Using the hen as our model we will investigate the use flaxseed diet as a way to prevent and suppress ovarian cancer.
|Dikshit, Anushka; Hales, Karen; Hales, Dale Buchanan (2017) Whole flaxseed diet alters estrogen metabolism to promote 2-methoxtestradiol-induced apoptosis in hen ovarian cancer. J Nutr Biochem 42:117-125|
|Dikshit, Anushka; Gao, Chunqi; Small, Carrie et al. (2016) Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries. J Steroid Biochem Mol Biol 159:73-85|
|Dikshit, Anushka; Gomes Filho, Manoel Adrião; Eilati, Erfan et al. (2015) Flaxseed reduces the pro-carcinogenic micro-environment in the ovaries of normal hens by altering the PG and oestrogen pathways in a dose-dependent manner. Br J Nutr 113:1384-95|
|Lengyel, E; Burdette, J E; Kenny, H A et al. (2014) Epithelial ovarian cancer experimental models. Oncogene 33:3619-33|
|Hales, Karen H; Speckman, Sheree C; Kurrey, Nawneet K et al. (2014) Uncovering molecular events associated with the chemosuppressive effects of flaxseed: a microarray analysis of the laying hen model of ovarian cancer. BMC Genomics 15:709|
|Eilati, Erfan; Hales, Karen; Zhuge, Yan et al. (2013) Flaxseed enriched diet-mediated reduction in ovarian cancer severity is correlated to the reduction of prostaglandin E(2) in laying hen ovaries. Prostaglandins Leukot Essent Fatty Acids 89:179-87|
|Eilati, Erfan; Bahr, Janice M; Hales, Dale Buchanan (2013) Long term consumption of flaxseed enriched diet decreased ovarian cancer incidence and prostaglandin E?in hens. Gynecol Oncol 130:620-8|
|Eilati, Erfan; Pan, Lurui; Bahr, Janice M et al. (2012) Age dependent increase in prostaglandin pathway coincides with onset of ovarian cancer in laying hens. Prostaglandins Leukot Essent Fatty Acids 87:177-84|