title: Salinomycin Induces Reactive Oxygen Species and Apoptosis in Aggressive Breast Cancer Cells as Mediated with Regulation of Autophagy.
abstract: Chemotherapy is a critical option for cancer treatment. However, consistent exposure to chemotherapeutic drugs promotes chemoresistance in cancer cells through diverse mechanisms. Accordingly, we investigated whether salinomycin, a monocarboxylic ionophore, could induce apoptosis in aggressive breast cancer cells or not, as well as its underlying mechanism.
  
  
  
  Using salinomycin on two breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, caspase-3/9 activity, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assayed.
  
  
  
  In this study, salinomycin induced apoptosis and autophagy in MDA-MB-231 cells. Salinomycin-mediated ROS production led to mitochondrial dysfunction in MDA-MB-231 cells. Interestingly, treatment of N-acetyl-L-cysteine (NAC), a scavenger of ROS, attenuated salinomycin-induced apoptosis and autophagy. Moreover, autophagy inhibition is involved in acceleration of apoptosis induced by salinomycin.
  
  
  
  Salinomycin induced apoptosis and ROS production, that were blocked by autophagy, thus resulting in protecting cancer cells. This crosstalk of two different physiological responses (autophagy and apoptosis) induced by salinomycin might play pivotal roles in the relationship between autophagy and apoptosis of cancer cells.
authors.affiliation: Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.
authors.forename: Kwang-Youn
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea.
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, 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, 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, Republic of Korea.
authors.forename: Deokjae
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Infectious Diseases, Armed Forces Medical Research Institute, Daejeon, Republic of Korea.
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Noh
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, 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, Republic of Korea ahnsc@pusan.ac.kr.
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000095662:Polyether Polyketides
chemical_list: D000900:Anti-Bacterial Agents; D011714:Pyrans; D017382:Reactive Oxygen Species; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: ROS; apoptosis; autophagy; breast cancer; chemoresistance; salinomycin