Abstract

Abstract For the past four decades, dietary fat intake has composed a significant portion of the typical Western diet, at 33-35% of total kilocalories. Approximately 8% of this dietary fat is from consumption of deep fat fried foods. Oil has been demonstrated to be absorbed by food during frying and contributes between 8 to 40% of the food’s final weight. As oils are used and reused for frying, complex chemical reactions take place creating deleterious polar compounds (e.g., acrylamide, sterol derivatives, or other reactive oxidative species.) Although these compounds are associated with health risks, i.e., heart disease, diabetes mellitus, and cancer, there is no regulation in the United States for upper limits of polar material in frying oil. This raises an important question as to whether thermally abused fryer oil (TAFO) can alter metastatic breast cancer progression. We initially conducted an in vivo study in which a modest amount of dietary fat, 25% of kilocalories, came from fresh fryer oil or TAFO. Ovariectomized BALB/C mice fed the diet containing TAFO for 16 weeks and inoculated with luciferase-expressing 4T1 murine mammary cancer cells had significantly more metastasis to lungs than control-fed animals (p < 0.05, n=21). Serum metabolic analysis in these animals revealed significantly elevated levels of fumarate, a known onco-metabolite, in TAFO-fed compared with control-fed animals (p < 0.05, n=9). To confirm that fumarate was mechanistically involved in metastatic progression, we conducted in vitro studies. 4T1 cells exposed to 500 nM to 10 µM monomethyl fumarate (MMF), a cell-permeable form of fumarate, trended toward an increase in the healing rate over 24 hours in a wound healing (scratch) assay compared to control (n =2). This preliminary evidence supports the hypothesis that fumarate accumulation creates a protumorigenic and metastatic environment and needs confirmation in subsequent investigation. This information can help elucidate mechanistic details of the effects of TAFO on breast cancer metastasis. Further work will assess rates of 4T1 cellular proliferation and invasion induced by MMF. In summary, dietary intake of TAFO increased metastasis of tumor cells to lungs, and dysregulation of the metabolite fumarate may be mechanistically involved. Citation Format: Jennifer R. Hughes, Kaitlyn M. Joyce, Anthony Cam, William G. Helferich, Zeynep Madak-Erdogan. Thermally abused frying oil enhances metastatic progression in vivo and in vitro: A link to elevated fumarate levels [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B26.

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