title: Proline Oxidase (POX) as A Target for Cancer Therapy.
abstract: Proline dehydrogenase/proline oxidase (PRODH/POX) is an enzyme catalyzing the first step of proline degradation, during which ROS and/or ATP is generated. POX is widely distributed in living organisms and is responsible for a number of regulatory processes such as redox homeostasis, osmotic adaptation, cell signaling and oxidative stress. Recent data provided evidence that POX plays an important role in carcinogenesis and tumor growth. POX may induce apoptosis in both intrinsic and extrinsic way. Due to ROS generation, POX may induce caspase-9 activity, which mediates mitochondrial apoptosis (intrinsic apoptosis pathway). POX can also stimulate TRAIL (tumor necrosis factorrelated apoptosis inducing ligand) and DR5 (death receptor 5) expression, resulting in cleavage of procaspase-8 and thus extrinsic apoptotic pathway. However, this tumor suppressor in certain environmental conditions may act as a prosurvival factor. Genotoxic, inflammatory and metabolic stress may switch POX from tumor growth inhibiting to tumor growth supporting factor. The potential mechanisms which may regulate switching of POX mode are discussed in this review.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kononczuk
authors.forename: Urszula
authors.initials: U
authors.lastname: Czyzewska
authors.forename: Joanna
authors.initials: J
authors.lastname: Moczydlowska
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Surażyński
authors.forename: Jerzy
authors.initials: J
authors.lastname: Palka
authors.affiliation: Department of Pharmaceutical Analysis, Medical University in Bialystok, ul. Adama Mickiewicza 2D, 15-222 Bialystok, Poland. wmiltyk@umb.edu.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Miltyk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D018384:Oxidative Stress / Q000502:physiology; D011392:Proline / Q000378:metabolism*; D011394:Proline Oxidase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D011392:Proline; D011394:Proline Oxidase