Branched-chain amino acids differentially affect proliferation, glucose-lactate metabolism and BCKDHA expression in human lung and pancreatic cancer cells
DOI:
https://doi.org/10.56782/pps.1050Keywords:
branched-chain amino acids, BCKDHA, cancer cell metabolism, glycolysis, amino acid catabolismAbstract
Branched-chain amino acids (BCAA) are increasingly discussed in the context of cancer metabolism and nutritional support, yet their effects on tumor cells remain insufficiently understood. This study determined how increased concentrations of leucine, isoleucine and valine affect proliferation, glucose–lactate metabolism, extracellular BCAA dynamics and BCKDHA expression in human lung (A549) and pancreatic (MIA PaCa-2) cancer cells and normal keratinocytes (HaCaT). Cells were cultured with individual BCAA or their mixtures at 1.5- and 2-fold higher concentrations than standard medium. Lower BCAA excess, particularly leucine, stimulated proliferation in both cancer cell lines, whereas higher concentrations, especially mixtures of all three amino acids, reduced cancer cell growth. A549 cells showed higher glucose consumption and lactate production than MIA PaCa-2 cells, indicating a more glycolytic phenotype, while pancreatic cancer cells displayed a distinct metabolic pattern despite comparable proliferation. Extracellular amino acid analysis revealed cell type-dependent differences in BCAA utilization, with A549 cells showing the highest depletion. Cancer cells generally exhibited lower BCKDHA expression than keratinocytes, suggesting reduced oxidative utilization of BCAA. These findings indicate that the biological effects of BCAA depend on concentration, composition and tumor type, and suggest that BCAA may support either anabolic or oxidative metabolic pathways depending on cellular context.
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Copyright (c) 2026 Julian Chrzanowski, Wojciech Graboń, Sebastian Granica, Miłosz Ludwinek, Aleksandra Zdanowicz, Beata Pyrzyńska, Marta Struga, Agnieszka Cudnoch-Jędrzejewska
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