Effects of Rhinacanthin-C on function and expression of efflux drug transporters in caco-2 cells

Abstract

Rhinacanthin-C is a bioactive naphthoquinone compound with several pharmacological actions such as anticancer and anti-inflammatory activities. The purposes of this study were to determine the effects of this compound on the function and expression of the ABC efflux transporters, in particular P-gp and MRP2, using the in vitro model of Caco-2 cells. The activities of P-gp and MRP2 were determined by following the intracellular accumulation of calcein and CDCF in the uptake assays. The expression of P-gp was monitored with the use of immunofluorescent probe against P-gp expressed on the cell surface. The results showed that rhinacanthin-C was able to inhibit the activities of both P-gp and MRP2. The inhibitory effect of this compound was more potent toward the function of P-gp than that of MRP2. The inhibition against P-gp activity was reversible. Treatment of the cells with rhinacanthin-C at the high concentration of 100 µM for 1 day was able to increase P-gp expression without any appreciable change in its function. At the highest non-cytotoxic concentration (0.625 µM) with 7 day treatment, rhinacanthin-C had no effect on both the expression and the function of P-gp. These findings suggested that concomitant uses of rhinacanthin-C and other P-gp drug substrates should be investigated further to evaluate the efficacy and safety.