Extracellular vesicles from tomatoes upregulate CYP1A1 mRNA content in differentiated Caco-2 cells

Cytochrome P450 enzymes (CYPs) from families 1 to 3 play a crucial role in the bioconversion and detoxification of various compounds. While the liver is a primary site for these enzymes, the small intestine also significantly contributes to first-pass metabolism. Many food-derived compounds are known to regulate CYP expression. However, it remains unclear whether plant-derived extracellular vesicles can influence CYP expression in intestinal epithelial cells. In this study, based on a previously generated transcriptomic dataset, we tested the hypothesis that tomato-derived extracellular vesicles can upregulate CYP1A1 mRNA levels in differentiated human Caco-2 cells. Further experiments confirmed that this effect is specific to differentiated Caco-2 cells and does not occur in other non-cancerous cell models or undifferentiated Caco-2 cells. The increase in CYP1A1 mRNA following treatment with extracellular vesicles was not accompanied by changes in the expression of CYP1A1-regulating transcription factors such as AhR and Sp1. In conclusion, this study is the first to demonstrate that plant-derived extracellular vesicles can affect first-pass metabolism by regulating the expression of cytochrome P450 enzymes.