Figure 2.

The purported effects of acute exercise in inducing ferroptosis in cancer cells. Hemolysis, as well as increased concentrations of hepcidin and CD8+ T-cells, are postulated to increase as a result of exercise. Increased hemolysis augments iron levels in the systemic circulation, which is taken up by TFR1 in cancer cells. Higher hepcidin levels decrease Fpn expression, and together with greater iron import, this leads to higher intracellular iron, contributing to greater ROS accumulation. Enhanced ROS accumulation stems from increased lipid peroxidation that attributes to a higher Fenton reaction rate. When coupled with greater CD8+ T-cell recruitment in the tumor milieu, higher concentrations of IFN-γ secreted is posited to cause considerably more hindrance to cystine uptake, which eventually leads to a lower production of the anti-oxidant enzyme, GPX4, to counteract ROS accumulation. Collectively, greater ROS production stemming from the effect of exercise ultimately amounts to a heightened propensity for cancer cell destruction via ferroptosis. TFR1, transferrin receptor 1; Fpn, ferroportin; ROS, reactive oxygen species; IFN-γ, interferon gamma; GPX4, glutathione peroxidase 4.