Pyridoxal 5'-Phosphate Suppresses Growth of Pancreatic Adenocarcinoma Cells In Vitro via Regulation of Oncogenic RAS.

Pancreatic cancer treatment typically involves surgery, chemotherapy, and radiotherapy. However, recent studies are investigating alternative therapeutic strategies, including targeted therapies, immunotherapy, and the adjunctive use of compounds like vitamin B6. PLP functions as a cofactor in over 100 enzymatic reactions crucial for amino acid metabolism, neurotransmitter production, and heme synthesis. Previous studies demonstrated PLP's anti-cancer properties in human lymphoma cells, demonstrating its anti-proliferative and anti-migratory effects, as well as its influence on cytokine levels and checkpoint marker expression. Herein, we further investigated PLP's anti-cancer effects on human pancreatic cancer cells, showing a reduction in cell growth, disruption of the mitochondrial membranes, increased superoxide production, and the induction of apoptosis. In addition, PLP treatment in BxPC3 cells affects transcripts related to key pathways like E2F, G2M Checkpoint, mTOR, and KRAS, enhancing functional protein networks that may improve anti-cancer effects. In PANC1 cells, PLP reduces KRAS-related transcripts and increases those involved in Tumor Necrosis Factor signaling and the unfolded protein response, suggesting a regulatory role that may enhance cellular stress responses. Overall, the findings from this study indicate that PLP may pave the way for more effective therapeutic adjunctive options in the management of pancreatic cancer.