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: Joanna Kononczuk, Urszula Czyzewska, Joanna Moczydlowska, Arkadiusz Surażyński, Jerzy Palka, Wojciech Miltyk
• Journal: Current drug targets (Curr Drug Targets) Vol. 16 Issue 13 Pg. 1464-9 ( 2015) ISSN: 1873-5592 [Electronic] United Arab Emirates
• PMID: 26553010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Reactive Oxygen Species
• Adenosine Triphosphate
• Proline
• Proline Oxidase

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Apoptosis (physiology)
• Humans
• Molecular Targeted Therapy
• Neoplasms (enzymology, pathology, therapy)
• Oxidative Stress (physiology)
• Proline (metabolism)
• Proline Oxidase (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (physiology)