Although abundant experimental evidences show that the Omega-3 polyunsaturated fatty acids (≥3-PUFAs) prevent carcinogenesis, the exact molecular mechanisms of the anti-cancer actions of α3-PUFAs in ovarian cancer remain incompletely understood. In the present study, the effectiveness of docosahexaenoic acid (DHA), a α3-PUFA, against ovarian cancer cells was investigated. We found that DHA induced cell cytotoxicity in three ovarian cancer cells including PA-1, MDAH2774 and ID8. DHA treatment inhibited the cell proliferation of PA-1 cells in a dose- and time-dependent manner. Meanwhile, DHA-treated ovarian cancer cells showed increased levels of caspase-3 activity, Annexin-V staining positive cells, TUNEL-positive cells and the portion of sub-G1 cells, suggesting that DHA-induced cell death is mainly associated with apoptosis. Western blot and immunocytochemistry assays revealed that DHA also remarkably increased the levels of phospho-ERK and phospho-JNK in both cytosol and nucleus. Moreover, knockdown ERK and JNK by small interfering RNAs partially attenuated the apoptosis induced by DHA, indicating that ERK and JNK activation is responsible for the apoptosis in DHA-treated ovarian cancer cells. In addition, we determined that the activation of ERK and JNK was associated with the reactive oxygen species (ROS) production induced by DHA. ROS scavenger, N-acetyl-L-cysteine (NAC), almost completely blocked the ERK and JNK phosphorylation as well as the apoptosis triggered by DHA. Together, these results indicate that DHA induces ROS and the ROS-dependent ERK and JNK activation is important to DHA-induced cell cytotoxicity in human ovarian cancer cells. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0006232 and 2011-0003060)].

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4175. doi:1538-7445.AM2012-4175