The Combination Of Beta-Cyclodextrin & 2-Deoxyglucose Worked Synergistically With Trail To Induce Apoptosis In 90% Of Panc-1 Cells At 10ng/Ml Of Trail

Since over 95% of pancreatic cancer cells express P-glycoprotein which could exclude chemotherapeutics from entering the cell, making it difficult to treat pancreatic cancer. To address this problem we used 2-deoxyglucose (2DG), beta-cyclodextrin (bCD) and TNFa-Related Apoptosis Inducing Ligand (TRAIL) combination to induce apoptosis in pancreatic cancer cells. 2DG can enter highly glycolytic cells through glucose transporters, while bCD could deplete cholesterol from the plasma membranes without entering the cell, inhibiting the signal transduction between PI3K and AKT, and TRAIL could activate TRAIL-receptors, activating caspases from outside. These three agents worked synergistically to induce apoptosis in Panc-1 pancreatic cancer cells; Panc-1 cells were incubated in medium containing 10 mM 2DG and 25 mM glucose for 90 minutes. Then 10 mM methyl-beta-cyclodextrin (MBCD) was added, and 30 minutes later, 10 ng/ml of TRAIL was added. 2 hours later, cells were washed and incubation continued. When cells were harvested 16 hours later, over 90% of cells were propidium iodide (PI) positive, while 0% of cells treated with TRAIL alone, and less than 30% of cells treated with 2DG-MBCD were PI positive. Citation Format: Ryuji Yamaguchi.{Authors}. The combination of beta-cyclodextrin u0026 2-deoxyglucose worked synergistically with TRAIL to induce apoptosis in 90% of Panc-1 cells at 10ng/ml of TRAIL. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B65.