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.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Kononczuk J,Czyzewska U,Moczydlowska J,Surażyński A,Palka J,Miltyk W

doi

10.2174/138945011613151031150637

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

1464-9

issue

13

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-71489

journal_volume

16

pub_type

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