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Fish fatty acids alter markers of apoptosis in colorectal adenoma and adenocarcinoma cell lines but fish consumption has no impact on apoptosis-induction ex vivo

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Abstract

Previous studies suggest that the n-3 polyunsaturated fatty acids (PUFAs) eicosapenteinoic acid (EPA) and docosahexaenoic acid (DHA), constituents of fish oil, exert chemopreventive activity in colon cancer. One of the mechanisms involved is the facilitation of apoptosis. While a pro-apoptotic potential of n-3 PUFAs has been suggested, it is still unclear whether additional consumption of fish will also lead to comparable results. The aim of this study was to assess EPA- and DHA-mediated effects on endpoints of apoptosis and to use a novel biomarker-approach to measure modulation of apoptosis by consumption of fish. LT97 human colon adenoma and HT29 human colon adenocarcinoma cells were used to investigate modulation of apoptosis by EPA, DHA or linoleic acid (LA) using a set of endpoints, namely phosphatidylserine staining with Annexin-V (flow cytometry), Bcl-2 expression (Real-time RT–PCR), and Bid, caspase 3, 8 and 9 expression as well as PARP cleavage (Western Blot). Furthermore, faecal water (FW) of volunteers (n = 89) from a human trial intervening with fish was used to investigate changes in apoptosis by flow cytometry. DHA was more effective at inducing apoptosis than EPA. LT97 cells were more prone to DHA and EPA induced apoptosis than HT29 cells. Treatment of LT97 cells with FW from volunteers consuming fish did not result in any changes in apoptosis. Taken together, our results show that adenoma cells are highly susceptible to n-3 PUFA-induced apoptosis. By using a biomarker-approach (FW) to measure apoptosis-induction ex vivo no change in apoptosis after additional fish consumption was detectable.

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Acknowledgments

We are very grateful to all the people who kindly participated in the FISHGASTRO study. We thank the FISHGASTRO Study Group, particularly Gerda K. Pot (Division of Human Nutrition, Wageningen University, The Netherlands), Gosia Majsak-Newman and Dr. Linda J. Harvey (Institute of Food Research, Norwich, UK) for organising and carrying out the FISHGASTRO human study. Sylvia Thiele (Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University Jena, Germany) is acknowledged for technical assistance. This work was performed within the Integrated Research Project SEAFOODplus, contract No FOOD-CT-2004-506359. The financing of the work by the European Union is gratefully acknowledged.

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  1. Department of Nutritional Toxicology, Institute for Nutrition, Friedrich-Schiller-University Jena, Dornburger Straße 24, 07743, Jena, Germany

    Nina Habermann, Adrienne Schön & Michael Glei

  2. Nutrition and Gastrointestinal Health, Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, UK

    Elizabeth K. Lund

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  1. Nina Habermann
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Correspondence to Nina Habermann.

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Habermann, N., Schön, A., Lund, E.K. et al. Fish fatty acids alter markers of apoptosis in colorectal adenoma and adenocarcinoma cell lines but fish consumption has no impact on apoptosis-induction ex vivo. Apoptosis 15, 621–630 (2010). https://doi.org/10.1007/s10495-010-0459-y

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