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Free radicals, metals and antioxidants in oxidative stress-induced cancer.

Abstract

Oxygen-free radicals, more generally known as reactive oxygen species (ROS) along with reactive nitrogen species (RNS) are well recognised for playing a dual role as both deleterious and beneficial species. The "two-faced" character of ROS is substantiated by growing body of evidence that ROS within cells act as secondary messengers in intracellular signalling cascades, which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. The cumulative production of ROS/RNS through either endogenous or exogenous insults is termed oxidative stress and is common for many types of cancer cell that are linked with altered redox regulation of cellular signalling pathways. Oxidative stress induces a cellular redox imbalance which has been found to be present in various cancer cells compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. DNA mutation is a critical step in carcinogenesis and elevated levels of oxidative DNA lesions (8-OH-G) have been noted in various tumours, strongly implicating such damage in the etiology of cancer. It appears that the DNA damage is predominantly linked with the initiation process. This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process. Attention is focused on structural, chemical and biochemical aspects of free radicals, the endogenous and exogenous sources of their generation, the metal (iron, copper, chromium, cobalt, vanadium, cadmium, arsenic, nickel)-mediated formation of free radicals (e.g. Fenton chemistry), the DNA damage (both mitochondrial and nuclear), the damage to lipids and proteins by free radicals, the phenomenon of oxidative stress, cancer and the redox environment of a cell, the mechanisms of carcinogenesis and the role of signalling cascades by ROS; in particular, ROS activation of AP-1 (activator protein) and NF-kappaB (nuclear factor kappa B) signal transduction pathways, which in turn lead to the transcription of genes involved in cell growth regulatory pathways. The role of enzymatic (superoxide dismutase (Cu, Zn-SOD, Mn-SOD), catalase, glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E, carotenoids, thiol antioxidants (glutathione, thioredoxin and lipoic acid), flavonoids, selenium and others) in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors, including Ref-1, NF-kappaB, AP-1 are also reviewed.

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  • Authors+Show Affiliations

    ,

    Faculty of Chemical and Food Technology, Slovak Technical University, SK-812 37 Bratislava, Slovakia. marian.valko@stuba.sk

    , , ,

    Source

    Chemico-biological interactions 160:1 2006 Mar 10 pg 1-40

    MeSH

    Animals
    Antioxidants
    Carcinogens
    DNA Damage
    Free Radicals
    Gene Expression Regulation, Neoplastic
    Humans
    Metals, Heavy
    Neoplasms
    Oxidative Stress
    Reactive Nitrogen Species
    Reactive Oxygen Species
    Signal Transduction

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    16430879

    Citation

    Valko, M, et al. "Free Radicals, Metals and Antioxidants in Oxidative Stress-induced Cancer." Chemico-biological Interactions, vol. 160, no. 1, 2006, pp. 1-40.
    Valko M, Rhodes CJ, Moncol J, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006;160(1):1-40.
    Valko, M., Rhodes, C. J., Moncol, J., Izakovic, M., & Mazur, M. (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-biological Interactions, 160(1), pp. 1-40.
    Valko M, et al. Free Radicals, Metals and Antioxidants in Oxidative Stress-induced Cancer. Chem Biol Interact. 2006 Mar 10;160(1):1-40. PubMed PMID: 16430879.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Free radicals, metals and antioxidants in oxidative stress-induced cancer. AU - Valko,M, AU - Rhodes,C J, AU - Moncol,J, AU - Izakovic,M, AU - Mazur,M, Y1 - 2006/01/23/ PY - 2005/10/15/received PY - 2005/12/15/revised PY - 2005/12/20/accepted PY - 2006/1/25/pubmed PY - 2006/3/29/medline PY - 2006/1/25/entrez SP - 1 EP - 40 JF - Chemico-biological interactions JO - Chem. Biol. Interact. VL - 160 IS - 1 N2 - Oxygen-free radicals, more generally known as reactive oxygen species (ROS) along with reactive nitrogen species (RNS) are well recognised for playing a dual role as both deleterious and beneficial species. The "two-faced" character of ROS is substantiated by growing body of evidence that ROS within cells act as secondary messengers in intracellular signalling cascades, which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. The cumulative production of ROS/RNS through either endogenous or exogenous insults is termed oxidative stress and is common for many types of cancer cell that are linked with altered redox regulation of cellular signalling pathways. Oxidative stress induces a cellular redox imbalance which has been found to be present in various cancer cells compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. DNA mutation is a critical step in carcinogenesis and elevated levels of oxidative DNA lesions (8-OH-G) have been noted in various tumours, strongly implicating such damage in the etiology of cancer. It appears that the DNA damage is predominantly linked with the initiation process. This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process. Attention is focused on structural, chemical and biochemical aspects of free radicals, the endogenous and exogenous sources of their generation, the metal (iron, copper, chromium, cobalt, vanadium, cadmium, arsenic, nickel)-mediated formation of free radicals (e.g. Fenton chemistry), the DNA damage (both mitochondrial and nuclear), the damage to lipids and proteins by free radicals, the phenomenon of oxidative stress, cancer and the redox environment of a cell, the mechanisms of carcinogenesis and the role of signalling cascades by ROS; in particular, ROS activation of AP-1 (activator protein) and NF-kappaB (nuclear factor kappa B) signal transduction pathways, which in turn lead to the transcription of genes involved in cell growth regulatory pathways. The role of enzymatic (superoxide dismutase (Cu, Zn-SOD, Mn-SOD), catalase, glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E, carotenoids, thiol antioxidants (glutathione, thioredoxin and lipoic acid), flavonoids, selenium and others) in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors, including Ref-1, NF-kappaB, AP-1 are also reviewed. SN - 0009-2797 UR - https://www.unboundmedicine.com/medline/citation/16430879/Free_radicals_metals_and_antioxidants_in_oxidative_stress_induced_cancer_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(05)00433-3 DB - PRIME DP - Unbound Medicine ER -