title: Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells.
abstract: Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore. It was reported to anticancer activity on various cancer cell lines. In this study, salinomycin was examined on apoptosis and autophagy through generation of reactive oxygen species (ROS) in osteosarcoma U2OS cells. Apoptosis, autophagy, mitochondrial membrane potential (MMP) and ROS were analyzed using flow cytometry. Also, expressions of apoptosis- and autophagy-related proteins were determined by western blotting. As a result, salinomycin triggered apoptosis of U2OS cells, which was accompanied by change of MMP and cleavage of caspases-3 and poly (ADP-ribose) polymerase. And salinomycin increased the expression of autophagy-related protein and accumulation of acidic vesicular organelles (AVO). Salinomycin-induced ROS production promotes both apoptosis and autophagy, as evidenced by the result that treatment of N-acetyl-l-cysteine (NAC), a ROS scavenger, attenuated both apoptosis and autophagy. In addition, inhibition of autophagy by 3-methyladenine (3 MA) enhanced the salinoymcin-induced apoptosis. Taken together, these results suggested that salinomycin-induced autophagy, as a survival mechanism, might be a potential strategy through ROS regulation in cancer therapy.
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Orthopedic Surgery, Headong Hospital, Busan 606-063, Republic of Korea.
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea.
authors.forename: Kwang-Youn
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea.
authors.forename: Sun-Nyoung
authors.initials: SN
authors.lastname: Yu
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 Food Science, International University of Korea, Jinju 660-759, Republic of Korea.
authors.forename: Sung-Sik
authors.initials: SS
authors.lastname: Chun
authors.affiliation: Department of Infectious Diseases, Armed Forces Medical Research Institute, Daejeon 305-878, Republic of Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Noh
authors.affiliation: Department of Orthopedic Surgery, Pusan National University School of Medicine, Busan 602-739, Republic of Korea.
authors.forename: Jeung-Tak
authors.initials: JT
authors.lastname: Suh
authors.affiliation: Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 626-870, Republic of Korea. Electronic address: ahnsc@pusan.ac.kr.
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D011714:Pyrans / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000095662:Polyether Polyketides
chemical_list: D000903:Antibiotics, Antineoplastic; D007476:Ionophores; D011714:Pyrans; D017382:Reactive Oxygen Species; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Apoptosis; Autophagy; Reactive oxygen species; Salinomycin; U2OS cells