Hyperglycemic conditions modulate the response of colon cancer cells to the mycotoxins alternariol and deoxynivalenol in vitro

A hyperglycemic condition, characterized by high glucose concentration in the bloodstream, is one of the most potent dietary risk factors for colorectal cancer (CRC). It regulates the response to oxidative stress, migration, and invasion of CRC cells, as well as affects the integrity of the intestinal barrier, which plays a pivotal role in protecting against chemicals and contaminants present in the diet. Although the molecular mechanisms underlying the toxicity of the mycotoxins deoxynivalenol (DON) and alternariol (AOH) are quite well-known, no research so far has considered the possibility that high glucose concentration might affect the response of CRC cells to mycotoxins. In this study, we evaluated how high glucose condition (50 mmol/L) modulates the effect of two mycotoxins distinct in toxicity and underlying mechanisms: DON (0.1–1 μmol/L) and AOH (0.1–20 μmol/L). We evaluated the migration and invasion in Caco-2 and HT-29 CRC cell lines, impact on barrier integrity and metabolism of mycotoxins in an intestinal in vitro co-culture model comprising Caco-2/HT-29-MTX-E12/CCD-18Co. Our results showed that high glucose concentration indeed modulates the response of CRC cells to mycotoxins, affecting their metabolism and altering the cellular sensitivity towards them. This observation shed new light on the importance of the involvement of different physiological and pathological conditions when considering the toxicity of mycotoxins. • AOH and DON modulate glucose receptors expression in CRC cells. • AOH and DON affect the migration and invasiveness of CRC cells. • High glucose modulates the effect of AOH and DON on CRC invasiveness. • High glucose increases AOH and DON- modulated intestinal integrity. • High glucose affects AOH metabolism as well as AOH and DON recovery.