This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fruehauf, J. P. Articles by Meyskens, F. L. Search for Related Content PubMed PubMed Citation Articles by Fruehauf, J. P. Articles by Meyskens, F. L., Jr.

Reactive Oxygen Species: A Breath of Life or Death?

Authors' Affiliation: Departments of Medicine and Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, California

Requests for reprints: John P. Fruehauf, Hematology/Oncology, University of California, Irvine, Cancer Center, Building 55, Room 321, 101 City Drive Cancer Center, Orange, CA 92668. Phone: 714-456-6310; Fax: 714-456-7668; E-mail: jfruehau{at}uci.edu.

Abstract

New insights into cancer cell–specific biological pathways are urgently needed to promote development of rationally targeted therapeutics. Reactive oxygen species (ROS) and their role in cancer cell response to growth factor signaling and hypoxia are emerging as verdant areas of exploration on the road to discovering cancer's Achilles heel. One of the distinguishing and near-universal hallmarks of cancer growth is hypoxia. Unregulated cellular proliferation leads to formation of cellular masses that extend beyond the resting vasculature, resulting in oxygen and nutrient deprivation. The resulting hypoxia triggers a number of critical adaptations that enable cancer cell survival, including apoptosis suppression, altered glucose metabolism, and an angiogenic phenotype. Ironically, recent investigations suggest that oxygen depletion stimulates mitochondria to elaborate increased ROS, with subsequent activation of signaling pathways, such as hypoxia inducible factor 1, that promote cancer cell survival and tumor growth. Because mitochondria are key organelles involved in chemotherapy-induced apoptosis induction, the relationship between mitochondria, ROS signaling, and activation of survival pathways under hypoxic conditions has been the subject of increased study. Insights into mechanisms involved in ROS signaling may offer novel avenues to facilitate discovery of cancer-specific therapies. Preclinical and clinical evaluation of agents that modify ROS signaling in cancer offers a novel avenue for intervention. This review will cover recent work in ROS-mediated signaling in cancer cells and its potential as a target for developmental therapeutics.

This article has been cited by other articles:

				C. Piccoli, R. Scrima, M. Ripoli, M. Di Ianni, B. Del Papa, A. D'Aprile, G. Quarato, M. P. Martelli, G. Servillo, C. Ligas, et al. Transformation by Retroviral Vectors of Bone Marrow-Derived Mesenchymal Cells Induces Mitochondria-Dependent cAMP-Sensitive Reactive Oxygen Species Production Stem Cells, November 1, 2008; 26(11): 2843 - 2854. [Abstract] [Full Text] [PDF]

				Y. Sun and B. Rigas The Thioredoxin System Mediates Redox-Induced Cell Death in Human Colon Cancer Cells: Implications for the Mechanism of Action of Anticancer Agents Cancer Res., October 15, 2008; 68(20): 8269 - 8277. [Abstract] [Full Text] [PDF]

				A. R. Hussain, M. Ahmed, N. A. Al-Jomah, A. S. Khan, P. Manogaran, M. Sultana, J. Abubaker, L. C. Platanias, K. S. Al-Kuraya, and S. Uddin Curcumin suppresses constitutive activation of nuclear factor-{kappa}B and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines Mol. Cancer Ther., October 1, 2008; 7(10): 3318 - 3329. [Abstract] [Full Text] [PDF]

				N. R. Khawaja, M. Carre, H. Kovacic, M. A. Esteve, and D. Braguer Patupilone-Induced Apoptosis Is Mediated by Mitochondrial Reactive Oxygen Species through Bim Relocalization to Mitochondria Mol. Pharmacol., October 1, 2008; 74(4): 1072 - 1083. [Abstract] [Full Text] [PDF]

				N. P. Degtyareva, L. Chen, P. Mieczkowski, T. D. Petes, and P. W. Doetsch Chronic Oxidative DNA Damage Due to DNA Repair Defects Causes Chromosomal Instability in Saccharomyces cerevisiae Mol. Cell. Biol., September 1, 2008; 28(17): 5432 - 5445. [Abstract] [Full Text] [PDF]

				R. A. El-Zein, M. Fenech, M. S. Lopez, M. R. Spitz, and C. J. Etzel Cytokinesis-Blocked Micronucleus Cytome Assay Biomarkers Identify Lung Cancer Cases Amongst Smokers Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1111 - 1119. [Abstract] [Full Text] [PDF]