Multidrug resistance （MDR） in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein （P-gp） is an ATP-binding cassette transporter frequently expressed in multidrug resistant tumor cells, inducing MDR. To reverse P-gp dependent MDR, anticancer drugs can be administered with P-gp inhibitors. Piperine and （R）-（＋）-citronellal both are P-gp inhibitors from dietary sources. In the present study, we aimed to evaluate the MDR reversal effects of piperine and （R）-（＋）-citronellal in multidrug resistant MCF-7/DOX cells. The results of cytotoxicity studies indicated that piperine and （R）-（＋）-citronellal both could abate the resistance of MCF-7/DOX after 72-h incubation. After 72-h incubation, piperine could dose-dependently down-regulate the MDR1 expression at the mRNA level, while （R）-（＋）-citronellal had no effect on the MDR1 expression. Therefore, piperine and （R）-（＋）-citronellal both could reverse MDR in MCF-7/DOX cells, and the reversal effect ofpiperine was related to dose-dependent down-regulation of the MDR1 expression at the mRNA level.
