NF-E2-related transcription factor-2 (Nrf2) is a key transcriptional factor regulating antioxidant gene expression and protection from oxidant damage. Docosahexaenoic acid (DHA) as one of ω3-polyunsaturated fatty acids has anticancer action through several mechanisms. Here we report that DHA-induced Nrf2 is related to cell death, not survival in HeLa cell. We confirmed DHA-induced apoptotic cell death using PARP cleavage, Anexin V staing, and TUNEL positive staining assay. DHA-triggering ROS production increased the level Nrf2 and decreased keap1 in dose- and time-dependent manner. Increased Nrf2 by DHA was partially Keap1 dependent. DHA activated Nrf2 signaling by increasing its translation and the Nrf2 was translocated from cytosol to nucleus. Upregulation of DHA-mediated Nrf2 was also confirmed by increase of heme oxygenase-1 (HO-1) expression. DHA-induced Nrf2 increased the level of Kruppel-like factor 9 (klf9) and then decreased thioredoxin reductase 2 (Txnrd2) in dose- and time-dependent manner. These results suggest that DHA-induced ROS increases Nrf2 and the Nrf2 is related to cell death by increase of klf9 and decrease of Txnrd2 in HeLa cells. Thus, utilization of ω3-PUFAs may represent a promising therapeutic approach for chemoprevention and treatment of human cervical cancer [This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF-2015R1D1A1A01056887) and by the framework of international cooperation program managed by National Research Foundation of Korea (2015K2A2A6002008)]

Citation Format: Kaipeng Jing, Soyeon Shin, Seung-Hyeon Han, Young-Joo Jeon, Jun-Young Heo, Gi-Ryang Kweon, Seung-Kiel Park, Jong-Il Park, Kyu Lim. Docosahexaenoic acid-induced Nrf2 may be correlated with cell death by amplification of oxidative stress via induction of klf9 in cervical cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2324.