NMR Analysis of Lactate Production via Alanine Metabolism in Pancreatic Ductal Adenocarcinoma Cells*

Pancreatic ductal adenocarcinoma (PDAC) is a type of pancreatic cancer with a high recurrence rate due to its aggressive nature and resistance to treatments. MIA-paCa-2 cells, derived from human PDAC, are used to investigate metabolic changes in pancreatic cancer cells. Glucose is the primary substrate driving cancer cell proliferation. Specifically, glucose rapidly produces pyruvate through glycolysis, which is then converted to lactate through Lactate Dehydrogenase. However, studies suggest that in the absence of glucose, alanine may contribute to the pyruvate pools and lactate production. The mechanism uses Alanine Transaminase and transfers an amino group from alanine to α-ketoglutarate, resulting in pyruvate and glutamate. Although MIA PaCa-2 cells are in a glycolytic environment, alanine can contribute to the acidic tumor microenvironment. This study utilized [1-13C] Alanine and Nuclear Magnetic Resonance Spectroscopy to investigate and track alanine metabolism in MIA-paCa-2 cells for 48 hrs in the absence of glucose. We hypothesized that alanine will serve as an auxiliary energy source to the production of lactate in certain conditions, although it is significantly less compared to the use of glucose. The preliminary results of this study will be presented and discussed.