title: Monoamine oxidase A (MAO A) inhibitors decrease glioma progression.
abstract: Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Kushal
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.
authors.forename: Weijun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.
authors.forename: Vijaya Pooja
authors.initials: VP
authors.lastname: Vaikari
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kota
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.|Program for Cancer Biology and Drug Discovery, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tzu-Shao
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Niyati
authors.initials: N
authors.lastname: Jhaveri
authors.affiliation: Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Groshen
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
authors.forename: Bogdan Z
authors.initials: BZ
authors.lastname: Olenyuk
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.
authors.forename: Florence M
authors.initials: FM
authors.lastname: Hofman
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.|Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.|USC-Taiwan Center for Translational Research, Los Angeles, California, USA.|Program for Cancer Biology and Drug Discovery, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Shih
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D000077204:Temozolomide; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008996:Monoamine Oxidase Inhibitors; D003606:Dacarbazine; D008995:Monoamine Oxidase; D000077204:Temozolomide
keywords: MAO A; MAO A inhibitors; TMZ-resistant; glioma; near-infrared dye conjugate