Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells

Iuchi,Katsuya; Ema,Mika; Suzuki,Moe; Yokoyama,Chikako; Hisatomi,Hisashi

doi:10.3892/mmr.2019.9940

Oxidized unsaturated fatty acids induce apoptotic cell death in cultured cells

Authors:
- Katsuya Iuchi
- Mika Ema
- Moe Suzuki
- Chikako Yokoyama
- Hisashi Hisatomi
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Affiliations: Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, Tokyo 180‑8633, Japan, Department of Biochemical Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992‑8510, Japan
Published online on: February 5, 2019 https://doi.org/10.3892/mmr.2019.9940
Pages: 2767-2773
Copyright: © Iuchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Polyunsaturated fatty acids are oxidized by non‑enzymatic or enzymatic reactions. The oxidized products are multifunctional. In this study, we investigated how oxidized fatty acids inhibit cell proliferation in cultured cells. We used polyunsaturated and saturated fatty acids, docosahexaenoic acid (DHA; 22:6), eicosapentaenoic acid (EPA; 20:5), linoleic acid (LA; 18:2), and palmitic acid (16:0). Oxidized fatty acids were produced by autoxidation of fatty acids for 2 days in the presence of a gas mixture (20% O2 and 80% N2). We found that oxidized polyunsaturated fatty acids (OxDHA, OxEPA and OxLA) inhibited cell proliferation much more effectively compared with un‑oxidized fatty acids (DHA, EPA and LA, respectively) in THP‑1 (a human monocytic leukemia cell line) and DLD‑1 (a human colorectal cancer cell line) cells. In particular, OxDHA markedly inhibited cell proliferation. DHA has the largest number of double bonds and is most susceptible to oxidation among the fatty acids. OxDHA has the largest number of highly active oxidized products. Therefore, the oxidative levels of fatty acids are associated with the anti‑proliferative activity. Moreover, caspase‑3/7 was activated in the cells treated with OxDHA, but not in those treated with DHA. A pan‑caspase inhibitor (zVAD‑fmk) reduced the cell death induced by OxDHA. These results indicated that oxidized products from polyunsaturated fatty acids induced apoptosis in cultured cells. Collectively, the switch between cell survival and cell death may be regulated by the activity and/or number of oxidized products from polyunsaturated fatty acids.

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