ROLE OF Β-ALANINE IN TRANSFORMING GEMCITABINE CHEMO-RESPONSE IN PANCREATIC CANCER

Introduction: Gemcitabine efficacy, is often limited due to its poor intra-cellular metabolism and chemo-resistivity. We hypothesized that β-alanine might improve intra-cellular uptake via buffering acidic surrounding.  We... [ view full abstract ]

Introduction: Gemcitabine efficacy, is often limited due to its poor intra-cellular metabolism and chemo-resistivity. We hypothesized that β-alanine might improve intra-cellular uptake via buffering acidic surrounding.  We aimed to evaluate the role of b-alanine towards increasing in vitro chemo-response of gemcitabine for the pancreatic cancer treatment. Methods: Using 1D-NOESY, 40 different metabolites were profiled from 3 pancreatic cell lines.  We observed changes in b-alanine concentration, with and without gemcitabine treatment in panc-1 cell lines.  To validate the cell-viability due to beta-alanine mediated drug performance, MTS assays were executed, which showed improved gemcitabine efficacy in comparison to control groups.  Migration and invasion assays were assessed in all groups in addition to flow-cytometry to assess cell cycle and apoptosis.  The experiment has been internally validated via repetition, triplicate cultures with pH measurement and reproducible metabolic profiles. Results: Global metabolic profiling of gemcitabine-resistant, Panc-1 cells, showed a decrease in the concentration of beta-alanine after treatment.   In presence of beta alanine, we observed the cell viability due to gemcitabine was reduced by 20%.  Likewise, the flow cytometry data showed panc1 cell-apoptosis increased by 2.5 % (P<0.05), with the combination therapy than with the gemcitabine alone; while Scratch assays showed significantly decreased migration of cells. Currently, we are validating the role of beta alanine towards buffering gemcitabine uptake by pancreatic cancer cells. Conclusion:  We have demonstrated that B-Alanine in Panc-1 cells improved efficacy of gemcitabine by decreased viability on MTS assay and increased apoptosis with decreased migration and invasion.