An update on schistosomicide and tumoricide in the future: arachidonic acid

Blood-dwelling schistosomes and cancer severely impact human health, welfare, and survival, essentially because of their ability to evade host immune cells and humoral effectors. The host immune defenses interact with the surface membrane of the worm and tumor cell. Schistosomes use their sphingomyelin (SM)-rich outer lipid bilayer to form with the surrounding water molecules a tight hydrogen bond in which they open, at will, pores that allow entry of nutrients but not lethal complement components and antibodies. In parasite-free humans, impaired expression of one or more cellular genes linked to lipid metabolism may allow the accumulation of SM at the plasma membrane. Drastic changes in surface membrane fluidity, permeability and integrity deprive the cell from its defense mechanisms and promote chaos in the signals it receives and emits, notably those controlling proliferation and locomotion. The hydrolysis of SM at the surface membrane of schistosomes and cancer cells to phosphocholine and the pro-apoptotic ceramide is feasible via the activation of membrane-associated neutral sphingomyelinase (nSMase). Arachidonic acid (ARA), a critical nutrient for all organisms and cells, is a powerful nSMase activator. Accordingly, ARA is the safest molecule for preventing schistosome and tumor cell development and growth. If readily accessible for human use in terms of availability and cost effectiveness, ARA could be considered a schistosomicide and tumoricide in the future. • Increased sphingomyelin content at the surface of schistosomes and preneoplastic cells is a key player in immune evasion. • SM hydrolysis is feasible via the activation of surface membrane-associated neutral sphingomyelinase via arachidonic acid. • Surface membrane SM hydrolysis elicits proapoptotic ceramide accumulation, and eventual schistosome and tumor cell death. • ARA does not kill all schistosome eggs in vivo, but readily eliminates larval stages in the intermediate and final hosts. • ARA elicits cancer cell apoptosis, but is readily converted to inflammatory metabolites after chemo- and radiotherapy. • ARA could safely be used in the future for cancer prophylaxis, and treatment immediately upon clinical detection.