The cytotoxic effect of crocin and chrysin on the AsPC-1 pancreatic cancer cell line is related to inhibition of nutrient uptake

Pancreatic cancer (PC) is one of the most common causes of cancer-related death. One of the hallmarks of cancer cells consists in metabolic reprogramming, which includes the Warburg effect (“aerobic glycolysis”), “glutamine addiction” and “lactate shuttle” and are associated with overexpression in GLUT1 (facilitative glucose transporter 1), ASCT2 (alanine, serine and cysteine transporter 2) and MCT1 (monocarboxylate transporter 1). These cancer hallmarks offer advantages to cancer cell proliferation but also creates metabolic vulnerabilities that can be therapeutically targeted. In this work, we evaluated the effect of some carotenoids (astaxanthin, β-carotene, crocin and fucoxanthin) and polyphenols (chrysin, genistein, kaempferol and quercetin) on glucose (³H-DG), lactic acid (³H-L) and glutamine (³H-GLN) uptake by two PC cell lines, AsPC-1 and PANC-1 cell lines. Of the tested compounds, crocin and chrysin were the compounds with the more marked inhibitory effects. Crocin promoted a decrease in both ³H-DG and ³H-L uptake (10–20 %) and chrysin promoted a decrease in ³H-DG and ³H-GLN uptake ( ± 20 %) by AsPC-1 cells. We further verified that crocin and chrysin do not significantly alter GLUT1, ASCT2 and MCT1 gene expression, and that their cytotoxic effect is not changed by GLUT1, MCT1 and ASCT2 inhibitors. In conclusion, crocin and chrysin decrease AsPC-1 cell viability, most likely due to their inhibitory effect on glucose, lactic acid and glutamine uptake.