title: Monensin Induces PC-3 Prostate Cancer Cell Apoptosis via ROS Production and Ca2+ Homeostasis Disruption.
abstract: Monensin is a carboxyl polyether ionophore that potently inhibits the growth of various cancer cells. Recently, the anticancer effects of monensin have been recognized based on its ability to induce apoptosis in cancer cells. However, anticancer effect of monensin and its mechanism of action have yet to be investigated, especially against human prostate cancer cells.
  
  
  
  Cell viability assay, western blot, cell-cycle arrest, annexin V/propidium iodide assay, reactive oxygen species (ROS) production and intracellular Ca2+flux were assayed.
  
  
  
  In this study, monensin significantly inhibited cell viability in a dose-dependent manner in prostate cell lines. Moreover, cell growth inhibition by monensin induced G1phase cell-cycle arrest and apoptosis via regulation of cell cycle- and apoptosis-related proteins in PC-3 cells. In addition, monensin induced the production of ROS and the disruption of Ca2+homeostasis, that was restored by diphenyleneiodonium, a mitochondrial ROS inhibitor and verapamil, a Ca2+channel blocker, respectively, as confirmed by pro-caspase-3 activation and poly ADP ribose polymerase cleavage.
  
  
  
  Monensin induces cell-cycle arrest and apoptosis through regulation of cell cycle- and apoptosis-related proteins, resulting in induction of mitochondrial ROS- and Ca2+-dependent apoptosis, respectively.
authors: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors: Sang-Hun
authors: SH
authors: Kim
authors: Department of Herbal Formula, Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.
authors: Kwang-Youn
authors: KY
authors: Kim
authors: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors: Sun-Nyoung
authors: SN
authors: Yu
authors: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors: Sul-Gi
authors: SG
authors: Park
authors: Department of Parasitology, Pusan National University School of Medicine, Yangsan, Republic of Korea.|Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors: Hak-Sun
authors: HS
authors: Yu
authors: School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea ahnsc@pusan.ac.kr ykseo@unist.ac.kr.
authors: Young-Kyo
authors: YK
authors: Seo
authors: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea ahnsc@pusan.ac.kr ykseo@unist.ac.kr.|Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors: Soon-Cheol
authors: SC
authors: Ahn
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D008985:Monensin; D002118:Calcium
keywords: Ca2+ homeostasis; ROS production; apoptosis; monensin