Abstract 2031: Effect of 2-Deoxyglucose on colorectal cancer cell lines

Abstract

Abstract Aerobic glycolysis (Warburg Effect) has long been regarded as a hallmark of many types of cancers. Colorectal cancer is known to exist in hypoxic conditions and hence, it is believed that most of the colorectal carcinoma tumors depend more on glycolysis than other tumors. A number of drugs have been developed in the past to target the up-regulated glycolytic pathway of the tumor cells, including 2-Deoxy-glucose (2DG). Being structurally similar to D-Glucose, it is utilized in the glycolytic pathway and is phosphorylated to 2DG-phosphate, which starts to accumulate in the cells. The accumulated 2DG-phosphate, inhibits key glycolysis enzymes - hexokinase and phospho-glucoisomerase leading to inhibition of glycolysis, and thus starving the cells of ATP. Although this has been regarded as the major mechanism of 2DG, various observations question this being the sole mechanism of action. To further investigate the molecular mechanism of 2DG, we studied its effect on colorectal carcinoma cell lines (GC3/Cl, SW620 and SW480) alone or in combination with 5-fluorouracil (5FU). We have observed that colorectal carcinoma cells are highly susceptible to 2DG compared to other cancer cells or non-cancerous cells and exert an additive effect in combination with 5FU. 2DG treatment arrested cell cycle at G1/G0 checkpoint and promoted apoptosis. The treatment of 2DG also resulted in a transient increase in the expression of p21. A reduced expression of other cell cycle proteins such as cyclin D1 and cyclin A was also observed following the 2DG treatment. Here, we provide evidence that in colorectal carcinoma cell lines, the 2DG causes a cell cycle arrest in addition to glycolysis inhibition and this additional activity may be responsible for an increased susceptibility of colorectal cancer cell lines to 2DG. 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 2031. doi:1538-7445.AM2012-2031