title: MAOA-a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells.
abstract: Autophagy and apoptosis are two well-controlled mechanisms regulating cell fate. An understanding of decision-making between these two pathways is in its infancy. Monoamine oxidase A (MAOA) is a mitochondrial enzyme that is well-known in psychiatric research. Emerging reports showed that overexpression MAOA is associated with prostate cancer (PCa). Here, we show that MAOA is involved in mediating neuroendocrine differentiation of PCa cells, a feature associated with hormone-refractory PCa (HRPC), a lethal type of disease. Following recent reports showing that NED of PCa requires down-regulation of repressor element-1 silencing transcription factor (REST) and activation of autophagy; we observe that MAOA is a novel direct target gene of REST. Reactive oxygen species (ROS) produced by overexpressed MAOA plays an essential role in inhibiting apoptosis and activating autophagy in NED PCa cells. MAOA inhibitors significantly reduced NED and autophagy activation of PCa cells. Our results here show MAOA as a new decision-maker for activating autophagy and MAOA inhibitors may be useful as a potential therapy for neuroendocrine tumors.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: UC Davis Cancer Center, University of California, Davis, CA 95616, USA.
authors.forename: Mel
authors.initials: M
authors.lastname: Campbell
authors.affiliation: Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.|Department of Urology, School of Medicine, and Shu-Tien Urological Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzu-Ping
authors.initials: TP
authors.lastname: Lin
authors.affiliation: Department of Pathology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Pan
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsin-Chen
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.|USC-Taiwan Center for Translational Research, University of Southern California, Los Angeles, CA 90089, USA.|Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, 1975 Zonal Ave., Los Angeles, CA 90033, USA.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Shih
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.|Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Chang
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D063306:Mitophagy; D008954:Models, Biological; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D060787:Neoplasm Grading; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor