Abstract 5440: Upregulation of prostaglandin E2 and TGF-alpha by linoleic acid enhances pro-oncogenic signaling in models of human lung and breast cancer

Abstract

Abstract The omega-6 polyunsaturated fatty acid (PUFA), linoleic acid (LA), has been reported to have adverse affects in the growth and metastasis of a variety of cancer cell models. However, there has been some controversy over how much these models relate to human disease. In the current study, a novel cascade of actions behind the LA-induced upregulation of cell proliferation has been identified. It is well established that PUFAs serves as precursors for eicosanoids, and LA supplementation was found to significantly increase the levels of Prostaglandin E2 (PGE2) in a variety of lung and breast cancer cell lines. These increases in PGE2 are associated with elevations in the activity of Cyclooxygenase-2 (COX-2), increased levels of Tumor Growth Factor-alpha (TGF-alpha) and specific pro-proliferative signaling pathways. These findings were corroborated in animal xenografts derived from the same cell lines used for the in vitro studies, with serum levels of PGE2 showing significant increases in PGE2 in animals fed diets high in LA. Moreover, the omega-3 PUFA, docosahexaenoic acid (DHA), was found to have an opposing affect on PGE2 production by upregulating Thromboxane B2 (TXB2), a stable metabolite of Thromboxane A2 (TXA2), which inhibits COX-2 activity. These findings present specific mechanisms behind the upregulation of cancer cell growth due to LA supplementation that may contribute to a resolution in determining its role in human disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5440. doi:1538-7445.AM2012-5440