APE1/Ref-1role in redox signaling: Translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

The heterogeneity of most cancers diminishes the treatment effectiveness of many cancer-killing regimens. Thus, treatments that hold the most promise are ones that block multiple signaling pathways essential to cancer survival. One of the most promising proteins in that regard is APE1, whose reduction-oxidation activity influences multiple cancer survival mechanisms, including growth, proliferation, metastasis, angiogenesis, and stress responses. With the continued research using APE1 redox specific inhibitors alone or coupled with developing APE1 DNA repair inhibitors it will now be possible to further delineate the role of APE1 redox, repair and protein-protein interactions. Previously, use of siRNA or over expression approaches, while valuable, do not give a clear picture of the two major functions of APE1 since both techniques severely alter the cellular milieu. Additionally, use of the redox-specific APE1 inhibitor, APX3330, now makes it possible to study how inhibition of APE1's redox signaling can affect multiple tumor pathways and can potentiate the effectiveness of existing cancer regimens. Because APE1 is an upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for agerelated macular degeneration and diabetic retinopathy. This paper reviews all of APE1's functions, while heavily focusing on its redox activities. It also discusses APE1's altered expression in many cancers and the therapeutic potential of selective inhibition of redox regulation, which is the subject of intense preclinical studies.

Original languageEnglish
Pages (from-to)36-53
Number of pages18
JournalCurrent Molecular Pharmacology
Volume5
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

DNA Repair
Oxidation-Reduction
Neoplasms
Proteins
Tumor Microenvironment
Macular Degeneration
Diabetic Retinopathy
Vascular Endothelial Growth Factor A
Small Interfering RNA
Neoplasm Metastasis
Growth
Research

Keywords

  • Age related macular degeneration
  • Base excision repair
  • Redox angiogenesis
  • Redox signaling
  • Reduction-oxidation
  • Tumor microenvironment

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Molecular Medicine

Cite this

@article{ff7fe3cd793a4c869d2521366d747a7c,
title = "APE1/Ref-1role in redox signaling: Translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1",
abstract = "The heterogeneity of most cancers diminishes the treatment effectiveness of many cancer-killing regimens. Thus, treatments that hold the most promise are ones that block multiple signaling pathways essential to cancer survival. One of the most promising proteins in that regard is APE1, whose reduction-oxidation activity influences multiple cancer survival mechanisms, including growth, proliferation, metastasis, angiogenesis, and stress responses. With the continued research using APE1 redox specific inhibitors alone or coupled with developing APE1 DNA repair inhibitors it will now be possible to further delineate the role of APE1 redox, repair and protein-protein interactions. Previously, use of siRNA or over expression approaches, while valuable, do not give a clear picture of the two major functions of APE1 since both techniques severely alter the cellular milieu. Additionally, use of the redox-specific APE1 inhibitor, APX3330, now makes it possible to study how inhibition of APE1's redox signaling can affect multiple tumor pathways and can potentiate the effectiveness of existing cancer regimens. Because APE1 is an upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for agerelated macular degeneration and diabetic retinopathy. This paper reviews all of APE1's functions, while heavily focusing on its redox activities. It also discusses APE1's altered expression in many cancers and the therapeutic potential of selective inhibition of redox regulation, which is the subject of intense preclinical studies.",
keywords = "Age related macular degeneration, Base excision repair, Redox angiogenesis, Redox signaling, Reduction-oxidation, Tumor microenvironment",
author = "Mark Kelley and Millie Georgiadis and Melissa Fishel",
year = "2012",
month = "1",
doi = "10.2174/1874467211205010036",
language = "English",
volume = "5",
pages = "36--53",
journal = "Current Molecular Pharmacology",
issn = "1874-4702",
publisher = "Bentham Science Publishers",
number = "1",

}

TY - JOUR

T1 - APE1/Ref-1role in redox signaling

T2 - Translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1

AU - Kelley, Mark

AU - Georgiadis, Millie

AU - Fishel, Melissa

PY - 2012/1

Y1 - 2012/1

N2 - The heterogeneity of most cancers diminishes the treatment effectiveness of many cancer-killing regimens. Thus, treatments that hold the most promise are ones that block multiple signaling pathways essential to cancer survival. One of the most promising proteins in that regard is APE1, whose reduction-oxidation activity influences multiple cancer survival mechanisms, including growth, proliferation, metastasis, angiogenesis, and stress responses. With the continued research using APE1 redox specific inhibitors alone or coupled with developing APE1 DNA repair inhibitors it will now be possible to further delineate the role of APE1 redox, repair and protein-protein interactions. Previously, use of siRNA or over expression approaches, while valuable, do not give a clear picture of the two major functions of APE1 since both techniques severely alter the cellular milieu. Additionally, use of the redox-specific APE1 inhibitor, APX3330, now makes it possible to study how inhibition of APE1's redox signaling can affect multiple tumor pathways and can potentiate the effectiveness of existing cancer regimens. Because APE1 is an upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for agerelated macular degeneration and diabetic retinopathy. This paper reviews all of APE1's functions, while heavily focusing on its redox activities. It also discusses APE1's altered expression in many cancers and the therapeutic potential of selective inhibition of redox regulation, which is the subject of intense preclinical studies.

AB - The heterogeneity of most cancers diminishes the treatment effectiveness of many cancer-killing regimens. Thus, treatments that hold the most promise are ones that block multiple signaling pathways essential to cancer survival. One of the most promising proteins in that regard is APE1, whose reduction-oxidation activity influences multiple cancer survival mechanisms, including growth, proliferation, metastasis, angiogenesis, and stress responses. With the continued research using APE1 redox specific inhibitors alone or coupled with developing APE1 DNA repair inhibitors it will now be possible to further delineate the role of APE1 redox, repair and protein-protein interactions. Previously, use of siRNA or over expression approaches, while valuable, do not give a clear picture of the two major functions of APE1 since both techniques severely alter the cellular milieu. Additionally, use of the redox-specific APE1 inhibitor, APX3330, now makes it possible to study how inhibition of APE1's redox signaling can affect multiple tumor pathways and can potentiate the effectiveness of existing cancer regimens. Because APE1 is an upstream effector of VEGF, as well as other molecules that relate to angiogenesis and the tumor microenvironment, it is also being studied as a possible treatment for agerelated macular degeneration and diabetic retinopathy. This paper reviews all of APE1's functions, while heavily focusing on its redox activities. It also discusses APE1's altered expression in many cancers and the therapeutic potential of selective inhibition of redox regulation, which is the subject of intense preclinical studies.

KW - Age related macular degeneration

KW - Base excision repair

KW - Redox angiogenesis

KW - Redox signaling

KW - Reduction-oxidation

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=84855822330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855822330&partnerID=8YFLogxK

U2 - 10.2174/1874467211205010036

DO - 10.2174/1874467211205010036

M3 - Article

C2 - 22122463

AN - SCOPUS:84855822330

VL - 5

SP - 36

EP - 53

JO - Current Molecular Pharmacology

JF - Current Molecular Pharmacology

SN - 1874-4702

IS - 1

ER -