Abstract B20: Modulation of a cancer lipogenic phenotype by dietary n-6/n-3 fatty acids in rat liver and colon cancer models

Abstract

Abstract Cancer development is a multistage process involving a breakdown of controlled processes such as cell differentiation, proliferation and apoptosis and regulatory feed-back mechanisms resulting in the characteristic rapid growth and metastases of cancer cells. The deregulation of cell growth and survival in cancer development has been associated with a distinct lipogenic phenotype involving cholesterol, phospholipids and fatty acids (FA). This phenotype is associated with changes in membrane structure and cellular oxidative status resulting in changes to membrane function, activity of enzymes and signal transduction pathways. Dietary components are associated with a protective effect against the development of certain cancers. Amongst these, dietary fat has been linked to either the promotion or prevention of cancer involving various biological mechanisms, depending on the type of fat and its FA content. The present study characterized the lipogenic phenotype in the liver and colon utilizing rat cancer models and the resultant modulation of membrane lipid components by dietary oils with specific fatty acid content. Sunflower oil (S) in combination with borage oil (B) and/or fish oil (F) was used to generate different n-6/n-3 FA ratios: SB (n-6/n-3: 38:1), SF (n-6/n-3: 13:1) and SBF (n-6/n-3: 10:1), while canola and olive oil were included as individual oil sources. In separate colon and liver in vivo cancer models, rats were fed the diets in respective groups and terminated whereupon liver and colon cancerous and respective adjacent normal tissue samples were collected for lipid and oxidative PCR micro-array analyses. The characteristic lipogenic phenotype associated with the growth and development of preneoplastic lesions involved a decrease in the phospholipid phosphatidylcholine / phosphatidylethanolamine (PC/PE) ratio, C20:4n-6 PC/PE ratio, n-3 polyunsaturated FA (PUFA) content and oxidative status. An interactive role of saturated FA, monounsaturated FA and C20:4n-6 appear to be a driving force sustaining altered growth characteristics in these lesions with a diet high in n-6 PUFA playing an underlying role. This characteristic phenotype was modulated by the dietary oils with varying n-6/n-3 FA ratios resulting in an increased n-3 PUFA tissue content, a higher lipid peroxidation level and altered growth of preneoplastic lesions. Depending on the specific stage of cancer development, dietary oil may either inhibit or stimulate the growth of preneoplastic lesions which appear to be related to differential changes in proliferative cell survival responses associated with an altered cellular redox status. Challenges in utilizing fatty acids in cancer modulation exist not only with regards to dietary sources and intake but also the effect on cell structure and modulation of signal transduction pathways governing altered growth responses in the prevention of cancer development. Therefore, the modulation of the lipid profile and oxidative status through dietary PUFA with a specific n-6/n-3 ratio may be an important chemopreventive tool in altering the growth characteristics of cancer cells. Citation Format: Stefan Abel, Celeste H. Abrahams, Maryna De Kock, Wentzel CA Gelderblom. Modulation of a cancer lipogenic phenotype by dietary n-6/n-3 fatty acids in rat liver and colon cancer models [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B20.