Phytoagents for Cancer Management: Regulation of Nucleic Acid Oxidation, ROS, and Related Mechanisms

Abstract

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.

Oxidative stress and DNA damage induced by spinosad exposure in Spodoptera frugiperda Sf9 cells

“…The radicals can directly react with DNA, or may indirectly act as signaling molecules to mediate DNA damage. Due to its low redox potential, guanine is the primary target of oxidation in DNA, which is a well-characterized marker for oxidative stress-induced DNA damage (Lee et al, 2013). We observed that increased 8-oxoG levels in the DNA of Sf9 cells after exposure to spinosad, and accompanied by upregulation of OGG1 and MTH1 expression (Figure 2).…”

“…Under conditions of oxidative stress, ROS altered the chemical properties of biomolecules, which causes oxidative insults such as proteins denaturation, lipids peroxidation and nucleic acids' oxidation (Lee, Huang, & Shyur, 2013). Cells present a variety of defense mechanisms to neutralize the oxidative damage; antioxidant enzymes SOD and CAT constitute the first line of defense against the toxic effects of superoxide radicals (Zhang, Wang, Sun, Fang, & Tang, 2016).…”

Solanine-induced reactive oxygen species inhibit the growth of human hepatocellular carcinoma HepG2 cells

“…This indicates that following treatment with solanine, the reduced cell growth observed may be due to enhanced cellular apoptosis. (26)(27)(28). The mitochondria of a eukaryotic cell are the main site for the production of ROS, and a large amount of ROS may be produced in the process of oxidative phosphorylation.…”

New Thiosemicarbazides and 1,2,4-Triazolethiones Derived from 2-(Ethylsulfanyl) Benzohydrazide as Potent Antioxidants

“…The conformer with the lowest electronic energy was used for calculation. The haemolytic BDE values were calculated by the following relationship, using the standard-state enthalpies at 1 atm and 298.15K: BDE = H radical + H H − H molecule (1) where H radical is the total enthalpy of the free radical, H H is the gas-phase total enthalpy of the hydrogen atom, and H molecule is the total enthalpy of the parent molecule.…”

“…radicals are commonly found in foods, drugs, and living systems. These ROS and free radicals may oxidise nucleic acids [1], denature proteins [2], and initiate the peroxidation of lipids [3] and the onset of degenerative diseases [4]. ROS are known to be the main cause of the aging process by their oxidation of cells and tissues [5].…”