Abstract
Omega-3 polyunsaturated fatty acids (PUFAs), such as those found in fish oil, are thought to have anti-tumorigenic effects and may help to treat and prevent cancer, including ovarian cancer. Thus, we aimed to evaluate the potential of docosahexaenoic acid (DHA), an omega-3 PUFA, as a therapeutic agent in ovarian cancer cell lines and a transgenic mouse model of ovarian cancer. DHA significantly inhibited cellular proliferation, induced cell cycle arrest and caused apoptosis in Hey and IGROV-1 cells. Pre-treatment with the anti-oxidant, N-acetylcysteine (NAC), reversed DHA-induced caspase 3 activity and prevented DHA-reduced cell proliferation. DHA also induced cellular reactive oxygen species (ROS) and inhibited adhesion and invasion in IGROV-1 and Hey cells. Furthermore, treatment with DHA demonstrated anti-tumorigenic and anti-invasive activity in a K18-gT121 +/-; p53fl/fl; Brca1fl/fl mouse model of ovarian cancer including downregulation of Ki67 and VEGF expression. The data provide a preclinical rationale for applying DHA for dietary intervention and therapeutic adjunct in patients with ovarian cancer.