Monoamine oxidase A (MAO A) inhibitors decrease glioma progression

• Published in: Oncotarget Vol. 7; no. 12; pp. 13842 - 13853
• Main Authors: Kushal, Swati, Wang, Weijun, Vaikari, Vijaya Pooja, Kota, Rajesh, Chen, Kevin, Yeh, Tzu-Shao, Jhaveri, Niyati, Groshen, Susan L, Olenyuk, Bogdan Z, Chen, Thomas C, Hofman, Florence M, Shih, Jean C
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 22.03.2016
• Subjects: Animals; Antineoplastic Agents, Alkylating - pharmacology; Apoptosis - drug effects; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Proliferation - drug effects; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Disease Progression; Drug Resistance, Neoplasm - drug effects; Drug Synergism; Glioma - drug therapy; Glioma - metabolism; Glioma - pathology; Humans; Male; Mice; Mice, Nude; Monoamine Oxidase - chemistry; Monoamine Oxidase Inhibitors - pharmacology; Research Paper; Temozolomide; Tumor Cells, Cultured; Xenograft Model Antitumor Assays; near-infrared dye conjugate; TMZ-resistant; glioma; MAO A inhibitors; MAO A
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.7283

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.