CancerDialysis and Ferroptosis
Author: Sture Hobro
Ferroptosis is a type of cell death that is of outstanding importance for the function of radiotherapy and chemotherapy in cancer treatment.
Pro-oxidative forces play a role in balancing oxidized PUFA (Poly Unsaturated Fatty Acids ) after radiation and chemo therapies. If oxidized PUFA levels get too high, it leads to ferroptosis. Anti-oxidative forces in cancer try to counteract this by protecting cancer from increased oxidized PUFA from those therapies. If cancer cells can successfully bolster enough antioxidant production to renew oxidized PUFA, cancer may avoid cell death during those therapies and be treatment resistant.
Glucose and glutamine are two important sources of energy for cancer cells and can help protect them from ferroptosis by increasing the production of NADPH through many metabolic pathways. NADPH together with the glutathione antioxidant pathway is important for protecting cancer cells from oxidative stress and further preventing ferroptosis in cancer. However, to handle oxidized PUFA, GPX4, a protein, plays a vital role in linking the glutathione antioxidant pathway to renewal of oxidized PUFA, and GPX4 connects glutathione the major hub for antioxidative forces in cancer cells for renewal of PUFA.
CancerDialysis will abruptly and considerably reduce the flow of the needed glucose and glutamine supply to uphold the antioxidant defense first by hampering the flow of NADPH to the glutathione metabolism, secondly by reducing the cysteine/ methionine and other amino acids inflow to cancer cells and CancerDialysis may therefore support radio and chemo therapies in their goal to kill cancer through ferroptosis.
Cystine, methionine and a few more amino acids can bolster the synthetization of glutathione and if the pool of glutathione (GSH and GSSG) is reduced the general antioxidant capacity in cancer cells will be reduced. During Cancer CancerDialysis all amino acids will be reduced and thereby reducing the antioxidant production capacity in cancer cells.
Therefore, CancerDialysis may promote ferroptosis and be an exemplary adjuvant treatment to radio and chemo therapies by boosting their ability to kill cancer through ferroptosis.
Figure: A weighing scale (a seesaw) depicts the fight between oxidative forces and antioxidative forces in cancer cells. If oxidative forces gets the upper hand and an accumulation of oxidized PUFA occurs cancer cells will start to die due to ferroptosis (green), by turning ferroptosis on. On the other hand, if cancer cells manage to bolster enough anti-oxidant force to handle the situation the cancer will survive and show signs of treatment resistance (red) by turning ferroptosis off.
