%0 Journal Article
%T Phytoagents for Cancer Management: Regulation of Nucleic Acid Oxidation, ROS, and Related Mechanisms
%A Wai-Leng Lee
%A Jing-Ying Huang
%A Lie-Fen Shyur
%J Oxidative Medicine and Cellular Longevity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/925804
%X Accumulation of oxidized nucleic acids causes genomic instability leading to senescence, apoptosis, and tumorigenesis. Phytoagents are known to reduce the risk of cancer development; whether such effects are through regulating the extent of nucleic acid oxidation remains unclear. Here, we outlined the role of reactive oxygen species in nucleic acid oxidation as a driving force in cancer progression. The consequential relationship between genome instability and cancer progression highlights the importance of modulation of cellular redox level in cancer management. Current epidemiological and experimental evidence demonstrate the effects and modes of action of phytoagents in nucleic acid oxidation and provide rationales for the use of phytoagents as chemopreventive or therapeutic agents. Vitamins and various phytoagents antagonize carcinogen-triggered oxidative stress by scavenging free radicals and/or activating endogenous defence systems such as Nrf2-regulated antioxidant genes or pathways. Moreover, metal ion chelation by phytoagents helps to attenuate oxidative DNA damage caused by transition metal ions. Besides, the prooxidant effects of some phytoagents pose selective cytotoxicity on cancer cells and shed light on a new strategy of cancer therapy. The ˇ°double-edged swordˇ± role of phytoagents as redox regulators in nucleic acid oxidation and their possible roles in cancer prevention or therapy are discussed in this review. 1. Nucleic Acid Oxidation as a Marker of Oxidative Insult by Reactive Oxygen Species and the Driving Force in Cancer Progression The integrity of the genome is of crucial importance for proper gene expression and DNA replication. Loss of genome integrity jeopardizes normal cellular physiological activities and leads to cellular pathological events such as senescence, apoptosis, and tumorigenesis [1]. Under oxidative stress, the level of genotoxic reactive oxygen species (ROS) is abnormally elevated. ROS interact with and modify the chemical properties of biomolecules inside the cell, which causes oxidative insults such as oxidation of nucleic acids, peroxidation of lipids [2], and denaturation of proteins [3]. Oxidative modification to DNA structure mainly occurs in the form of base oxidation. Guanine, which possesses the lowest oxidation potential of the DNA bases, is the most frequent target of ROS. ROS-elicited changes in biomolecules can be used as biomarkers to indicate the presence and extent of oxidative insult. 8-Oxo-7,8-dihydroguanine (8-oxoG), the oxidation product of the DNA base guanine is a well-characterized marker
%U http://www.hindawi.com/journals/omcl/2013/925804/