Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact.

To promote the potential of arachidonic acid (ARA) for cancer prevention and management, experiments were implemented to disclose the mechanisms of its tumoricidal action. Hepatocellular, lung, and breast carcinoma and normal hepatocytes cell lines were exposed to 0 or 50 μM ARA for 30 min and then assessed for proliferative capacity, surface membrane-associated sphingomyelin (SM) content, neutral sphingomyelinase (nSMase) activity, beta 2 microglobulin (β2 m) expression, and ceramide (Cer) levels. Reactive oxygen species (ROS) content and caspase 3/7 activity were evaluated. Exposure to ARA for 30 min led to impairment of the tumor cells' proliferative capacity and revealed that the different cell lines display remarkably similar surface membrane SM content but diverse responses to ARA treatment. Arachidonic acid tumoricidal impact was shown to be associated with nSMase activation, exposure of cell surface membrane β2 m to antibody binding, and hydrolysis of SM to Cer, which accumulated on the cell surface and in the cytosol. The ARA and Cer-mediated inhibition of tumor cell viability appeared to be independent of ROS generation or caspase 3/7 activation. The data were compared and contrasted to findings reported in the literature on ARA tumoricidal mechanisms.