Abstract 4405: A new energy restriction mimetic decreases survival and FOXM1 expression in pancreatic cancer cells

Abstract

Abstract Pancreatic cancer is a deadly disease with only 6% of the patients living longer than 5 years. Even if the disease is diagnosed when it is localized, the 5-year survival rate is approximately 19%. A characteristic of cancer cell metabolism is a shift from oxidative phosphorylation to aerobic glycolysis known as the Warburg effect. It is well known that calorie restriction (CR) is a powerful intervention that suppresses tumorigenesis in animal models by targeting glycolysis and oncogenic signaling pathways. Recent studies have shown that the metabolic responses characteristic of CR can be obtained with the use of energy restriction mimetics (ERM). The purpose of this study is to evaluate a new ERM, OSU-CG5 in altering growth of pancreatic cancer cells and nutrient-sensitive signaling pathways. Tumors including those of the pancreas have uncontrolled proliferation necessitating increased fuel demands by increasing glucose availability and altering metabolic signaling pathways. Since ERM have been reported to target glucose transport, we evaluated whether OSU-CG5 alters glucose transport (Glut) proteins and glucose uptake. Glut1, but not Glut2, 3, 4, and 6, were overexpressed in Panc-1 cells with a 6-fold higher expression compared to HPNE cells. Glut proteins were not altered in MiaPaca cells. OSU-CG5 did not alter Glut1 protein expression in either cell line. Silencing Glut1 also had no effect on the cytoxicity of OSU-CG5. OSU-CG5 did not alter glucose uptake when measured in different concentrations of glucose in the media. Cell survival, as measured with Pico green, was decreased after OSU-CG5 treatment with an IC 50 of 3uM when cultured in physiological concentration of 5 and 10mM of glucose. FOXM1 is unregulated in pancreatic cancer and a promoter of the Warburg effect. We found that OSU-CG5 significantly decreased expression of FOXM1 in Panc1 and MiaPaca cells. Our findings indicate that OSU-CG5 does not inhibit the growth of Panc1 and MiaPaca pancreatic cancer cells by decreasing glucose uptake but may target the FOXM1 signaling pathways. Citation Format: Laura Scolaro, Susan Lanza-Jacoby. A new energy restriction mimetic decreases survival and FOXM1 expression in pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4405. doi:10.1158/1538-7445.AM2017-4405