Role of Fe, Transferrin and Transferrin Receptor in Anti-Tumor Effect of Vitamin C

SIMPLE SUMMARY: High-dose vitamin C (VC) inhibits cell proliferation in a variety of tumors, which is mediated by ROS. Iron is an important factor in the Fenton reaction, in which H(2)O(2) reacts with ferrous iron to produce hydroxyl radicals, which may enhance the killing of tumor cells. In this study, we investigated the roles of iron level and the mainly pathway of iron uptake-TF/TFR system on VC-induced cytotoxicity. We conducted a preliminary evaluation of the potential value of (68)Ga-citrate imaging in the anti-tumor therapy of VC combined with iron supplementation. ABSTRACT: High-dose vitamin C (VC) exhibits anti-tumor effects, and the cytotoxicity of VC is correlated with oxidative stress. However, iron, as a redox metal, plays an important effect in redox cycling and free radical formation in cells. This study addresses the role of iron ion in the cytotoxicity of VC. We found that iron supplementation increases the anti-tumor effect of VC, which was influenced by the cellular iron uptake pathway–transferrin (TF)/transferrin receptor (TFR) system. The TFR expression of tumors can be assessed by (68)Ga-citrate PET imaging, and it would be helpful to screen out the tumor type which is more sensitive to VC combined with an iron supplementation treatment.