Curcumin potentiates the fungicidal effect of dodecanol by inhibiting drug efflux in wild-type budding yeast.

Drug resistance commonly occurs when treating immunocompromised patients who have fungal infections. Curcumin is a compound isolated from Curcuma longa. It has been reported to inhibit drug efflux in several human cell lines and non-pathogenic budding yeast Saccharomyces cerevisiae cells that overexpress the ATP-binding cassette transporters S. cerevisiae Pdr5p and pathogenic Candida albicans Cdr1p and Cdr2p. The aim of this study was to examine the effects of curcumin on multidrug resistance in a wild-type strain of the budding yeast with an intrinsic expression system of multidrug-efflux-related genes. The antifungal activity of dodecanol alone was temporary against S. cerevisiae; however, restoration of cell viability was completely inhibited when the cells were co-treated with dodecanol and curcumin. Furthermore, restriction of rhodamine 6G (R6G) efflux from the cells and intracellular accumulation of R6G were observed with curcumin treatment. Reverse transcription-polymerase chain reaction analysis revealed that curcumin reduced dodecanol-induced overexpression of the ABC transporter-related genes PDR1, PDR3, and PDR5 to their control levels in untreated cells. Curcumin can directly restrict glucose-induced drug efflux and inhibit the expression of the ABC transporter gene PDR5, and can thereby probably inhibit the efflux of dodecanol from S. cerevisiae cells. Curcumin is effective in potentiating the efficacy of antifungal drugs via its effects on ABC transporters. This article is protected by copyright. All rights reserved.