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Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin

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Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicinresistant MCF7/MDR human breast cancer cells. The results demonstrated that doxorubicinmediated cytotoxicity was significantly enhanced by salinomycin in the MCF7/MDR cells, and this occurred in a dosedependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycintreated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR1 and MRP1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapy.
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Document Type: Research Article

Affiliations: 1: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626870, Republic of Korea 2: Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626870, Republic of Korea 3: Genome Instability Research Center, Ajou University School of Medicine, Suwon, Gyeonggi-do 443721, Republic of Korea 4: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689798, Republic of Korea

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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