Reactive oxygen species and angiogenesis

NADPH oxidase as target for cancer therapy

Masuko Ushio-Fukai, Yoshimasa Nakamura

Research output: Contribution to journalArticle

350 Citations (Scopus)

Abstract

Angiogenesis is essential for tumor growth, metastasis, arteriosclerosis as well as embryonic development and wound healing. Its process is dependent on cell proliferation, migration and capillary tube formation in endothelia cells (ECs). High levels of reactive oxygen species (ROS) such as superoxide and H2O2 are observed in various cancer cells. Accumulating evidence suggests that ROS function as signaling molecules to mediate various growth-related responses including angiogenesis. ROS-dependent angiogenesis can be regulated by endogenous antioxidant enzymes such as SOD and thioredoxin. Vascular endothelial growth factor (VEGF), one of the major angiogenesis factor, is induced in growing tumors and stimulates EC proliferation and migration primarily through the VEGF receptor type2 (VEGFR2, Flk1/KDR). Major source of ROS in ECs is a NADPH oxidase which consists of Nox1, Nox2, Nox4, Nox5, p22phox, p47phox and the small G-protein Rac1. NADPH oxidase is activated by various growth factors including VEGF and angiopoietin-1 as well as hypoxia and ischemia, and ROS derived from this oxidase are involved in VEGFR2 autophosphorylation, and diverse redox signaling pathways leading to induction of transcription factors and genes involved in angiogenesis. Dietary antioxidants appear to be effective for treatment of tumor angiogenesis. The aim of this review is to provide an overview of the recent progress on role of ROS derived from NADPH oxidase and redox signaling events involved in angiogenesis. Understanding these mechanisms may provide insight into the NADPH oxidase and redox signaling components as potential therapeutic targets for tumor angiogenesis.

Original languageEnglish
Pages (from-to)37-52
Number of pages16
JournalCancer Letters
Volume266
Issue number1
DOIs
Publication statusPublished - Jul 18 2008

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NADPH Oxidase
Reactive Oxygen Species
Oxidation-Reduction
Endothelium
Neoplasms
Vascular Endothelial Growth Factor A
Cell Movement
Therapeutics
Antioxidants
Cell Proliferation
Angiopoietin-1
Vascular Endothelial Growth Factor Receptor
Thioredoxins
Monomeric GTP-Binding Proteins
Arteriosclerosis
Angiogenesis Inducing Agents
Growth
Superoxides
Wound Healing
Embryonic Development

Keywords

  • Angiogenesis
  • Cancer
  • NADPH oxidase
  • Reactive oxygen species
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Reactive oxygen species and angiogenesis : NADPH oxidase as target for cancer therapy. / Ushio-Fukai, Masuko; Nakamura, Yoshimasa.

In: Cancer Letters, Vol. 266, No. 1, 18.07.2008, p. 37-52.

Research output: Contribution to journalArticle

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