Phytoagents for cancer management: regulation of nucleic acid oxidation, ROS, and related mechanisms.
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 "double-edged sword" role of phytoagents as redox regulators in nucleic acid oxidation and their possible roles in cancer prevention or therapy are discussed in this review.
School of Science, Monash University Sunway Campus, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
Wai-Leng
WL
Lee
Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 115, Taiwan.
Jing-Ying
JY
Huang
Agricultural Biotechnology Research Center, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 115, Taiwan ; Graduate Institute of Pharmacognosy, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei 110, Taiwan ; Graduate Institute of Biotechnology, National Chung Hsing University, No. 250 Kuo Kuang Rd., Taichung 402, Taiwan.
Lie-Fen
LF
Shyur
D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009696:Nucleic Acids / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D064209:Phytochemicals / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism*
D009696:Nucleic Acids; D064209:Phytochemicals; D017382:Reactive Oxygen Species