Children with High Risk Neuroblastoma: Prophylactic and Therapeutic Treatment with Docosahexaenoic Acid
Despite intense multimodal treatment of neuroblastoma consisting of surgery, chemotherapy, radiotherapy, and stem cell rescue, long-term survival is only 50% in the high-risk group. We therefore need to improve existing treatment protocols and search for new medications.
Inflammation drives cancer growth, and targeted therapy that dampens inflammatory responses is anti-proliferative. The inducible COX-2 enzyme that converts the omega-6 fatty acid arachidonic acid (AA) to various inflammatory prostaglandins is up-regulated in neuroblastoma tissue. Non steroidal anti-inflammatory drugs (NSAIDs) that inhibit prostaglandin synthesis have profound growth inhibitory effects on neuroblastoma cells in preclinical models.
Omega-3 fatty acids oppose the effects of omega-6 fatty acids and have been implicated in cancer treatment and prevention. Omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors of anti-inflammatory compounds. From DHA and EPA resolvins and protectins are produced, which are potent pro-resolving lipid mediators essential for the clearance of inflammatory cells and mediators at an injured site.
This chapter will discuss the toxicity of DHA to neuroblastoma cells both in vivo and in vitro as well as discuss the effects of DHA in clinical trials of various cancers. In vivo, DHA is able to delay time to tumor development and reduce tumor growth in neuroblastoma xenograft models. In vitro, DHA acts by inducing mitochondrial-dependent apoptosis of neuroblastoma cell lines. In addition, clinical studies show that DHA acts in synergy with chemotherapy.
In summary, this chapter shows that omega-3 fatty acids such as DHA are possible new agents for neuroblastoma prevention and treatment, and suggests that these compounds be tested in clinical trials as adjuvant therapy to chemotherapeutic drugs in children with neuroblastoma.
KeywordsArachidonic Acid Neuroblastoma Cell Docosahexaenoic Acid Lipid Mediator Radical Oxygen Species
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