Abstract 3275: A novel approach to treat medulloblastoma: The omega-3 fatty acids DHA and EPA reduce medulloblastoma tumor growth in vitro and in vivo

Abstract

Abstract Background: The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exert antitumoral properties shown in several cancer types. DHA is found in abundance in the brain and is of importance in normal brain development and maintenance of function including cognitive functions. Medulloblastoma is the most common malignant CNS tumor of childhood. Intensive multimodal treatment is necessary including surgery, radiotherapy and chemotherapy. However, treatment often results in significant neurological sequelae and the risk of resistant relapses is still significant. The neuroprotective and antitumoral properties of omega-3 could therefore be of great benefit. Our aim was to investigate the effect of DHA and EPA on medulloblastoma in vitro and in vivo. Methods: In a panel of medulloblastoma cell lines the cytotoxic activity of DHA and EPA was studied using cell viability assays. The molecular mechanisms were characterized using cell- and molecular biology techniques. Mice with human medulloblastoma xenografts were treated with; DHA alone or with DHA and EPA for 30 days from time of tumor take while tumor growth was monitored. Control mice were fed with normal chow. The incorporation of fatty acids was analyzed in tumors, erythrocytes and brain tissue by LS-MS/MS. Results: DHA and EPA induced medulloblastoma cell toxicity with IC50 values ranging from 1.9 to 68 μM in six medulloblastoma cell lines. DHA reduced the prostaglandin E2 production, indicating a possible mechanism of action. In vivo, omega-3 supplementation resulted in significant reduction of tumor growth when established tumors were treated. DHA levels were increased in both tumor tissue and erythrocyte membrane compared to control. The in vivo treatment was non-toxic. Conclusions: DHA and EPA exert toxic effect on medulloblastoma cells in vitro and reduce tumor growth in vivo. These omega-3 fatty acids could therefore be good candidates for improving current therapy and at the same time protect healthy neurons from therapy-induced toxicity promoting cognitive function in survivors. Thus, omega-3 fatty acid supplementation has the potential of reducing tumor growth as well as reducing sequelae. Citation Format: Linda M. Ljungblad, John-Inge Johnsen, Malin Wickström, Per Kogner, Helena Gleissman. A novel approach to treat medulloblastoma: The omega-3 fatty acids DHA and EPA reduce medulloblastoma tumor growth in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3275. doi:10.1158/1538-7445.AM2015-3275