Individual and combined effects of roquefortine C and mycophenolic acid on human monocytic and intestinal cells

Abstract

Roquefortine C (ROC) and mycophenolic acid (MPA) are secondary metabolites produced by various fungal species. It is known that both ROC and MPA may co-occur in raw materials or food. However, to date there is a lack of information regarding their toxicity. In this study, ROC and/or MPA cytotoxicity was evaluated on human intestinal (Caco-2) and monocytic cell cultures (THP-1 and CD14+). After 48 h single mycotoxin exposure, viability tests showed that monocytes (THP-1 and CD14+) were more sensitive to ROC (inhibitory concentration 50% (IC50)=55 and 45 μM, respectively) than to MPA (IC50>780 μM). IC50 values determined from ROC and MPA mono-exposure experiments on Caco-2 cells were >100 and >780 μM, respectively. Caco-2 cell viability was significantly reduced after 48 h co-exposure at high ROC/MPA concentrations. A synergistic effect was observed at 10/78, 25/780 and 50/780 μM ROC/MPA concentrations, while an additive effect was seen at 100/780 μM. THP-1 apoptosis rate increased after 3 and/or 6 h single ROC (from 10 to 100 μM) and MPA (780 μM) exposures in a dose-dependent manner. Co-exposure to 100/780 μM of ROC/MPA led to an increase in the THP-1 apoptotic cell population. No apoptosis mechanism was observed on Caco-2 cells. This is the first time that combined ROC and MPA cytotoxic effects, as well as the associated mechanisms are investigated.