The Omega-3 Fatty Acids Dha And Epa Inhibit Medulloblastoma Growth

Background/Aim: Docosahexaenoic acid (DHA) and eicosapentaenic acid (EPA) are two essential omega-3 polyunsaturated fatty acid that have been shown to exert antitumoral effects in several cancer types, both in vitro and in vivo. DHA has also been shown to protect neural cells from apoptosis and is of importance in the maintenance of normal brain development and function. Medulloblastoma (MB) is the most common malignant brain tumor in children with a poor 5-year survival of only 50-60%. It is a highly invasive embryonal neuroepithelial tumor that arises in the cerebellum and has a tendency to disseminate throughout the CNS early in its course. Multimodal treatment is always necessary in the form of surgery, radiotherapy and chemotherapy. However, treatment for this disease often results in significant endocrinological and intellectual sequelae. The neuroprotective and antitumoral properties of omega-3 fatty acids could therefore be of great benefit in this patient group. Here we aim to investigate the effect of DHA and EPA in medulloblastoma. Methods: Cytotoxic activity of DHA and EPA was studied in cell viability assay in a panel of medulloblastoma cell lines. The molecular mechanisms were characterized using cell- and molecular biology techniques. Results: By adding different concentrations of DHA and EPA we could demonstrate IC50s ranging between 1.9 and 46 µM for DHA and 3.8 and 68 µM for EPA in the six examined medulloblastoma cell lines. All cell lines showed greater sensitivity for DHA than EPA. Preliminary data showed that treatment with DHA inhibited the prostaglandin E2 production in medulloblastoma cells, indicating a possible mechanism of action. Conclusions: Medulloblastoma cells are highly sensitive to omega-3 induced toxicity. Previous studies have showed that DHA can protect neurons from apoptosis. Therefore, omega-3 fatty acids are good candidates for improving medulloblastoma therapy by acting as both “sword and shield” by killing off cancer cells while protecting healthy neurons from therapy induced toxicity, thus possibly both inhibiting tumor growth and reducing the sequelae associated with other modes of brain tumor treatment. Citation Format: Linda M. Ljungblad, Malin Wickstrom, John-Inge Johnsen, Per Kogner, Helena Gleissman. The omega-3 fatty acids DHA and EPA inhibit medulloblastoma growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3988. doi:10.1158/1538-7445.AM2014-3988