The Caco-2 cell monolayer: usefulness and limitations

BACKGROUND: The Caco-2 monolayer has been used extensively for the high-throughput screening of drug permeability and identification of substrates, inhibitors, and inducers of intestinal transporters, especially P-glycoprotein (P-gp). Traditionally, the Caco-2 monolayer is viewed as a single barrier rather than a polarized cell monolayer consisting of metabolic enzymes that are sandwiched between two membrane barriers with distinctly different transporters. OBJECTIVE: This review addressed the usefulness and limitations of the Caco-2 cell monolayer in drug discovery and mechanistic studies. METHODS: This mini-review covered applications of the Caco-2 monolayer, clarified misconceptions, and critically addressed issues on data interpretation. CONCLUSION: The catenary model extends the usefulness of Caco-2 monolayer and provides proper mechanistic insight and data interpretation.