Superoxide dismutase: an emerging target for cancer therapeutics
- 1 December 2001
- journal article
- Published by Informa Healthcare in Emerging Therapeutic Targets
- Vol. 5 (6), 697-710
- https://doi.org/10.1517/14728222.5.6.697
Abstract
Superoxide dismutase (SOD) is a critical enzyme responsible for the elimination of superoxide radicals and is considered to be a key anti-oxidant in aerobic cells. Cellular consumption of oxygen is essential for oxidative phosphorylation during ATP generation in the mitochondria, yet this cellular metabolism also leads to the production of reactive oxygen species (ROS), including the superoxide radical (O2 • -) and hydrogen peroxide (H2O2). Accumulation of ROS results in cellular oxidative stress and, if not corrected, can lead to the damage of important biomolecules such as membrane lipids, proteins and DNA. Prolonged accumulation of high levels of free radicals in cells may cause irreversible cellular injury and ultimately result in cell death. Since SOD is the key enzyme in the first metabolic step of superoxide elimination, deficiency in SOD or inhibition of the enzyme activity may cause severe accumulation of O2 • - in cells and lead to cell death. Thus, inhibition of SOD may provide a novel way to kill cancer cells. Due to dysfunction in the regulation of cell growth, cancer cells are active in energy metabolism, and thus produce high levels of O2 • - and other ROS and are under constant oxidative stress. This may render the malignant cells more dependent on SOD to eliminate the toxic superoxide radicals and thus potentially more sensitive to SOD inhibitors. It is a plausible hypothesis that inhibition of SOD may preferentially kill malignant cells through a free radical-mediated mechanism. This article will review evidence that suggests SOD as an emerging therapeutic target for cancer treatment. The relevant clinical implications and potential risk will also be discussed.Keywords
This publication has 84 references indexed in Scilit:
- Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balanceThe Journal of Physiology, 2000
- Superoxide dismutase as a target for the selective killing of cancer cellsNature, 2000
- Oxidative stress and apoptosisPathophysiology, 2000
- A threshold concept for cancer therapyMedical Hypotheses, 2000
- Mitochondrial control of apoptosis: the role of cytochrome cBiochimica et Biophysica Acta (BBA) - Bioenergetics, 1998
- Generation of Putative Intrastrand Cross-Links and Strand Breaks in DNA by Transition Metal Ion-Mediated Oxygen Radical AttackChemical Research in Toxicology, 1997
- Structural Origins of Bulky Oxidative DNA Adducts (Type II I-Compounds) as Deduced by Oxidation of Oligonucleotides of Known SequenceChemical Research in Toxicology, 1996
- Superoxide and hydrogen peroxide in relation to mammalian cell proliferationFree Radical Biology & Medicine, 1995
- Effect of reactive oxygen species on lysosomal membrane integrityVirchows Archiv B Cell Pathology Including Molecular Pathology, 1993
- Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interleukin‐1, tumor necrosis factor, selected anticancer drugs, and ionizing radiationThe FASEB Journal, 1993