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.
Keywords: Apoptosis, cancer, proline dehydrogenase (PRODH), proline oxidase (POX).
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Current Drug Targets
Title:Proline Oxidase (POX) as A Target for Cancer Therapy
Volume: 16 Issue: 13
Author(s): Joanna Kononczuk, Urszula Czyzewska, Joanna Moczydlowska, Arkadiusz Surażyński, Jerzy Palka and Wojciech Miltyk
Affiliation:
Keywords: Apoptosis, cancer, proline dehydrogenase (PRODH), proline oxidase (POX).
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.
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Kononczuk Joanna, Czyzewska Urszula, Moczydlowska Joanna, Surażyński Arkadiusz, Palka Jerzy and Miltyk Wojciech, Proline Oxidase (POX) as A Target for Cancer Therapy, Current Drug Targets 2015; 16 (13) . https://dx.doi.org/10.2174/138945011613151031150637
DOI https://dx.doi.org/10.2174/138945011613151031150637 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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