Related Experiment Video
Updated: Jun 12, 2026
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
Reactive oxygen species abrogate the anticarcinogenic effect of eicosapentaenoic acid in Atm-deficient mice
Ralf Schubert1, Janine Reichenbach, Claudia Koch
1Children's Hospital I, Goethe-University, Frankfurt, Germany.
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.
Insights
Eicosapentaenoic acid (EPA) inhibits tumor cell proliferation and induces apoptosis in vitro. However, in Atm-deficient mice, EPA increased oxidative stress and DNA damage, negating its potential anticancer effects.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- n-3 polyunsaturated fatty acids, like eicosapentaenoic acid (EPA), show potential in suppressing cancer cell growth.
- Ataxia-telangiectasia (AT) is a genetic disorder linked to increased oxidative stress and cancer susceptibility.
- Ataxia-telangiectasia mutated (Atm)-deficient mice serve as a model for studying cancer development under oxidative stress.
Purpose of the Study:
- To investigate the impact of high-dose EPA on tumor development in Atm-deficient mice.
- To evaluate EPA's effects on cell proliferation, cell-cycle progression, apoptosis, and tumor latency.
- To assess EPA's influence on reactive oxygen species (ROS) generation and oxidative DNA damage (ODD) in this cancer model.
Main Methods:
- In vitro analysis of EPA's toxicity, proliferation, cell-cycle, and apoptosis effects on AT-4 tumor cells.
- In vivo assessment of EPA's effect on tumor latency in Atm-deficient mice.
- Measurement of ROS generation and ODD following EPA treatment in the mouse model.
Main Results:
- EPA demonstrated significant antiproliferative effects on AT-4 tumor cells in vitro, altering cell-cycle progression and inducing apoptosis.
- EPA treatment did not affect the latency to tumorigenesis in Atm-deficient mice.
- EPA administration led to a notable increase in ROS and ODD in Atm-deficient mice.
Conclusions:
- EPA exhibits direct antiproliferative and pro-apoptotic effects on tumor cells in vitro.
- In Atm-deficient mice, EPA treatment paradoxically increased oxidative stress and DNA damage, potentially counteracting its anticancer benefits.
- The pro-oxidant effects of EPA in vivo may abrogate its anticarcinogenic potential in genetic cancer models with elevated oxidative stress.
Related Concept Videos
01:20Radical Autoxidation
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...