Reactive Oxygen Species Abrogate the Anticarcinogenic Effect of Eicosapentaenoic Acid in Atm-Deficient Mice

Abstract

Recent studies have demonstrated that n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are able to suppress cell proliferation and inhibit tumor growth. The objective of our study was to investigate the influence of a high dose EPA on the development of the tumor phenotype in ataxia-telangiectasia mutated (Atm)-deficient mice, a genetic cancer model that is associated with increased levels of oxidative stress. We analyzed toxicity, proliferation, cell-cycle progression, and apoptosis of EPA in vitro and latency to tumorigenesis in vivo. Because of the impact of reactive oxygen species (ROS) on the tumor incidence in ataxia telangiectasia (AT), we further analyzed the effect of EPA on the generation of ROS and oxidative DNA damage (ODD). EPA effectively inhibited proliferation, altered cell-cycle progression, and induced apoptosis of tumor cells (AT-4). EPA showed no effect on the latency to tumorigenesis in Atm-deficient mice. EPA treatment was accompanied by a significant increase of ROS and ODD. Our results demonstrate the antiproliferative effect of EPA on tumor cells by alteration of cell-cycle progression and induction of apoptosis in vitro. On the other hand, EPA treatment of Atm-deficient mice led to the formation of ROS and accumulation of ODD that might have abrogated the anticarcinogenic effect caused by EPA.

Protective Effect of Fish Oil Supplementation on DNA Damage Induced by Cigarette Smoking

“…High intake of n-3 fatty acids diminishes the chemotactic responsiveness of neutrophils and monocytes ( 25 ) and decreases the production of free radicals ( 26 ). Some studies have concluded that there are some benefits of fish oil in oxidative damage to DNA ( 27 - 30 ). However, a recent study reported that EPA treatment in Atm-deficient mice led to the formation of reactive oxygen species and the accumulation of oxidative DNA damage ( 31 ).…”

Fish oil, polyphenols, and physical performance

“…Studies at the University of Tromso in Norway have shown that the industrial processes used to extract fish oil destroy or remove the trace ingredients in fish (such as the polyphenols) that likely played a critical role in conferring their original health benefits and certainly greatly reduced anti-inflammatory effects of the oil (Elvevoll, Osterud, 2003). In fact, the removal of antioxidants and other trace compounds creates a situation where the purified fish oils can become pro-oxidative (Sanders, hinds, 1992;Sen et al, 1997;Umegaki et al, 2001; Vericel at al., 2003; Schubert et al, 2010), pro-inflammatory (Mata et al, 1996;berstad et al, 2003), and cause increased DNA damage (Schubert et al, 2010). Worryingly, there is evidence that older subjectsthe bulk of those who take ω3 supplements -are intrinsically more vulnerable to its pro-oxidative effects (cazzola et al, 2007) probably because they are not eating enough of the appropriate antioxidants to compensate for the ω3's (Umegaki et al, 2001).…”

From alga to omega; have we reached peak (fish) oil?

“…[7][8][9][10][11][12][13][14] In certain situations such as heavy exercise, 8 high purified o3 highly unsaturated fatty acids intakes, 10,11,13 insufficient antioxidant cover 8,9 and significant pre-existing oxidative stress and/or inflammatory pathology, 8,13 this may create a pro-inflammatory environment, manifesting inter alia with increased DNA damage 9 and increased levels of soluble vascular cell adhesion molecule (sVCAM-1). 13 It is important to point out that others have found sVCAM-1 to be reduced; 15 the divergent findings may reflect different intakes of dietary ancillary factors in different populations.…”