Abstract 4113: Restricted ketogenic diet reduces growth and distant organ metastasis in the murine VM-M3 metastatic tumor model

Abstract

Abstract Metastasis involves the spread of tumor cells throughout the body and is one of the leading causes of cancer death. Most current drug therapies for metastatic cancer are toxic and only marginally effective in providing long-term management. Respiratory insufficiency with compensatory aerobic fermentation (Warburg effect) is the hallmark biochemical phenotype of nearly all neoplastic cells within tumors. Most tumor cells are incapable of utilizing ketone bodies for energy due to their respiratory insufficiency. Calorie restriction, which lowers blood glucose and elevates ketone bodies, is known to reduce tumor growth. We previously showed that ketogenic diets with high fat/protein + carbohydrate ratios of 3-4:1 are better able to lower blood glucose and elevate ketone levels than is calorie restriction alone. We evaluated the influence of a new ketogenic diet formula from Solace Nutrition (KetoGen) on the growth and metastatic spread of the VM-M3 tumor. VM-M3 is a highly metastatic macrophage-like tumor that arose spontaneously in the brain of the syngeneic inbred VM/Dk mouse strain. The VM-M3 cells spread rapidly (within days) to lungs, liver, spleen, kidney, and brain with 100% fidelity following subcutaneous implantation. Tumor bearing VM mice were fed either a standard lab chow diet in unrestricted amounts (SD-UR), a standard lab chow restricted to obtain an 18% reduction in body weight (SD-R), or the KetoGen diet restricted (KG-R) to match the body weights of the SD-R control group. Tumor size was significantly smaller and organ metastasis was significantly less in the KG-R group than in the SD-UR or SD-R groups. Although blood glucose was reduced similarly in both the SD-R and KG-R groups, blood ketones were 3-fold higher in the KG-R group than in the SD-R group. These results show that VM-M3 tumor growth and systemic metastasis was managed better with the restricted KetoGen KD than with calorie restriction of a high carbohydrate standard diet. As all human and mouse tumors cells suffer from respiratory insufficiency, our findings suggest that the KetoGen diet should be an effective non-toxic therapy against systemic metastatic cancer. Citation Format: Zeynep Akgoc, Laura M. Shelton, David Ryan, Xijun Zhu, Thomas N. Seyfried. Restricted ketogenic diet reduces growth and distant organ metastasis in the murine VM-M3 metastatic tumor model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4113. doi:10.1158/1538-7445.AM2014-4113