Abstract 4765: Investigation of omega-3 docosahexaenoic acid (DHA)-induced apoptosis in human triple negative breast cancer

Abstract

Abstract Omega-3 fatty acid enriched diets especially diets rich in docosahexaenoic acid (DHA) have long been associated with a lower incidence of a variety of cancers. Both in vivo and in vitro studies have indicated that DHA exerts anticancer actions via inducing tumor cells to undergo programmed cell death or decreasing cell proliferation. In this study, we investigated the anticancer actions of DHA in human triple negative breast cancer (TNBC) cells in vitro. Data indicate that DHA induces apoptosis in MDA-MB-231 and BT-20 human p53 mutant TNBC cells by activating both intrinsic and extrinsic death-mediating pathways. Activation of apoptosis is associated with induction of endoplasmic reticulum (ER) stress, and increased levels of phosphorylated JNK (pJNK), and CHOP and DR5 protein levels; as well as, reduced levels of pIκB and NF-κB downstream mediators: c-FLIP, Survivin and Bcl-2. DHA induces ROS generation and antioxidants, RRR-alpha tocopherol (αT) and N-acetyl-Cysteine (NAC) block DHA-induced apoptosis, ER stress and upregulation of pJNK/CHOP/DR5. Taken together, our data demonstrate that DHA induces apoptosis in p53 mutant TNBC via activation of ROS mediated ER stress and suppression of NF-kB mediated anti-apoptotic factors. Since p53 mutant TNBCs are associated with poor prognosis and limited treatment options, these studies suggest DHA may be a successful adjuvant treatment strategy. Research is supported by the Clayton Foundation for Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4765. doi:10.1158/1538-7445.AM2011-4765