title: Nitroxoline induces apoptosis and slows glioma growth in vivo.
abstract: BACKGROUND
  Nitroxoline is an FDA-approved antibiotic with potential antitumor activity. Here we evaluated whether nitroxoline has antiproliferative properties on glioma cell growth in vitro and in vivo using glioma cell lines and a genetically engineered PTEN/KRAS mouse glioma model.
  
  
  METHODS
  The effect of nitroxoline treatment on U87 and/or U251 glioma cell proliferation, cell-cycle arrest, invasion, and ability to induce an apoptotic cascade was determined in vitro. Magnetic resonance imaging was used to measure glioma volumes in genetically engineered PTEN/KRAS mice prior to and after nitroxoline therapy. Induction of apoptosis by nitroxoline was evaluated at the end of treatment using terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL).
  
  
  RESULTS
  Nitroxoline inhibited the proliferation and invasion of glioblastoma cells in a time- and dose-dependent manner in vitro. Growth inhibition was associated with cell-cycle arrest in G1/G0 phase and induction of apoptosis via caspase 3 and cleaved poly(ADP-ribose) polymerase. In vivo, nitroxoline-treated mice had no increase in tumor volume after 14 days of treatment, whereas tumor volumes doubled in control mice. Histological examination revealed 15%-20% TUNEL-positive cells in nitroxoline-treated mice, compared with ∼5% in the control group.
  
  
  CONCLUSIONS
  Nitroxoline induces apoptosis and inhibits glioma growth in vivo and in vitro. As an already FDA-approved treatment for urinary tract infections with a known safety profile, nitroxoline could move quickly into clinical trials pending confirmatory studies.
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Jelena
authors: J
authors: Lazovic
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Lea
authors: L
authors: Guo
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Jonathan
authors: J
authors: Nakashima
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Leili
authors: L
authors: Mirsadraei
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: William
authors: W
authors: Yong
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Hyun J
authors: HJ
authors: Kim
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Benjamin
authors: B
authors: Ellingson
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Hong
authors: H
authors: Wu
authors: Department of Radiological Sciences, Ronald Reagan UCLA Medical Center, Los Angeles, California (J.L., L.G., H.J.K., B.E., W.B.P.); Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (J.N., H.W.); Department of Pathology, University of California San Diego Medical Center, San Diego, California (L.M.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California (W.Y.); Department of Biostatistics, Fielding School of Public Health and Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (H.J.K.).
authors: Whitney B
authors: WB
authors: Pope
mesh_terms: D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D009600:Nitroquinolines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000892:Anti-Infective Agents, Urinary; D000970:Antineoplastic Agents; D009600:Nitroquinolines; C005308:nitroxoline
keywords: 8-hydroxy-5-nitroquinoline; PTEN; glioma animal model; invasion; nitroxoline