The Effect of Curcumin on P‐glycoprotein Function

Abstract

Multidrug resistance (MDR) is one of the leading cause of cancer treatment failure. P‐glycoprotein (P‐gp) has been reported as a major mechanism of MDR that increased the efflux of drugs. Three generations of P‐gp inhibitors have been developed, however, systemic toxicities limited the clinical application of these compounds. Therefore, identification of the potent and non‐toxic P‐gp inhibitors from natural products may be an alternative choice. The objective of this study was to investigate the inhibitory effect and molecular mechanism of curcumin on human P‐gp efflux function.HEK293 cell were stably transfected with human P‐gp. The MDR1 shift assay was applied to evaluate whether curcumin is a substrate of P‐gp. The effect of curcumin on P‐gp function was evaluated by rhodamine 123 accumulation assay and calcein AM uptake assay. Rhodamine 123 efflux assay was performed to analyze the inhibitory mechanism.Results from cytotoxicity assay and MDR1 shift assay indicated that curcumin is a safe natural product without cytotoxicity and not a P‐gp substrate. The intracellular fluorescence of rhodamine 123 was higher in curcumin treated P‐gp expressed cells than no‐treatment control, suggesting curcumin may inhibit P‐gp efflux function. Results of calcein‐AM uptake assay and rhodamine 123 efflux assay demonstrated that curcumin significantly inhibited P‐gp efflux function in dose dependent manner. Furthermore, curcumin uncompetitively inhibited rhodamine 123 efflux by P‐gp.This study demonstrated that curcumin, sourced from natural plants, as a potential P‐gp function modulator. Although the exploring of novel inhibitors from natural products is still in the early stages, the promising beginning and detailed mechanism investigation provided by this study will be helpful in the future in vivo studies and clinical use.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.