title: Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin.
abstract: 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 doxorubicin-resistant MCF-7/MDR human breast cancer cells. The results demonstrated that doxorubicin-mediated cytotoxicity was significantly enhanced by salinomycin in the MCF-7/MDR cells, and this occurred in a dose-dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin-treated 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 MDR-1 and MRP-1 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 MCF-7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapy.
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Kwang-Youn
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Sun-Nyoung
authors.initials: SN
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Suel-Ki
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Hyeun-Deok
authors.initials: HD
authors.lastname: Choi
authors.affiliation: Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Hak-Sun
authors.initials: HS
authors.lastname: Yu
authors.affiliation: Genome Instability Research Center, Ajou University School of Medicine, Suwon, Gyeonggi-do 443‑721, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Ji
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689‑798, Republic of Korea.
authors.forename: Young-Kyo
authors.initials: YK
authors.lastname: Seo
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea.
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D000095662:Polyether Polyketides
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides; C421109:multidrug resistance-associated protein 1