Ovarian Cancer Risk in Laying Hens Is Reduced by Dietary Polyunsaturated Fatty Acids: A Case for Redox Homeostasis and Reprogrammed Mitochondrial Metabolism in Ovarian Tumors (OR04-05-19)

Abstract

ObjectivesIn 2012, ovarian cancer accounted for 239,000 new cancer cases and 152,000 cancer-related deaths worldwide. Epidemiological studies around the world suggest that high dietary consumption of polyunsaturated fatty acids (PUFAs) reduces a woman’s odds of developing ovarian cancer. We hypothesize that PUFA-enriched diets will decrease ovarian cancer risk in White Leghorn laying hens. MethodsThe specific aim of our research was to investigate ovarian cancer risk and molecular events in ovarian tumors of White Leghorn laying hens consuming PUFA-enriched diets. We exposed laying hens to long-term (46-week) dietary PUFA treatment, using Whole Flaxseed (WFX), Flaxseed Oil (FXO), Fish Oil (FHO), Corn Oil (CNO), and a low-PUFA diet, Defatted Flaxseed (DFX). At the end of the dietary treatment we collected 88 ovarian tumors and conducted qPCR analysis for gene expression. ResultsIn comparison to a control diet lacking a PUFA supplement, the odds ratios of hens developing ovarian cancer decreased with PUFA enrichment (Odd Ratios: DFX = 0.74, WFX = 0.69, FXO = 0.61, FHO = 0.57, CNO = 0.57), corroborating human epidemiological observations of ovarian cancer risk. Gene expression analysis from hen ovarian tumors suggests that PUFA-rich diets (ie WFX, FXO, FHO, and CNO) improve mitochondrial electron transport chain function by upregulating Cytochrome B (Complex 3) and Cyctochrome C Oxidases 1, 2, and 3 (Complex 4), and likely reduce superoxide emission from Complex 1 as evidenced by the downregulation of NADH Dehydrogenase 2. PUFA enrichment also reduced the expression of enzymes associated with reactive oxygen species (ROS), reactive nitrogen species (RNS), and lipid peroxides, suggesting overall major improvement in the redox state of tumors from PUFA-enriched diets. The FXO diet was uniquely distinguished by increasing the expression of ATP5B1 (catalytic subunit of ATP Synthase) and the ADP/ATP Translocase (ANT1), suggesting increased mitochondrial cristae space and improved oxidative phosphorylation capacity in FXO-enriched ovarian tumors. ConclusionsDietary PUFA enrichment (omega-3 or omega-6) reduces end point risk for ovarian cancer in laying hens. The underlying etiology appears to center on decreasing oxidative stress and increasing mitochondrial function in ovarian tumors. Funding SourcesNational Institutes of Health.