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

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 68Ga-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.

Antioxidant Hydrogels: Antioxidant Mechanisms, Design Strategies, and Applications in the Treatment of Oxidative Stress‐Related Diseases

“…This, in turn, can incite oxidative stress and culminate in oxidative damage to cell membranes, proteins, nucleic acids, etc. [36] The mitigation of oxidative stress can be achieved by constraining the capacity of metal ions to participate in the generation and reaction of free radicals. A prevalent strategy involves employing chelating agents to envelop metal ions within a ligand-rich milieu, curbing their propensity to interact with other molecules.…”

Iron and Cancer: A Special Issue

“…Pharmacological ascorbate increases extracellular H 2 O 2 and DNA demethylation by activating ten-eleven translocation (TET) [ 12 ] and cytoplasmic labile iron with a positive feedback loop that amplifies toxicity in cancer cells [ 11 ]. Here, Qiu et al [ 13 ] demonstrate that high-dose ascorbate inhibited cellular proliferation in cancer cells, although sensitivity to ascorbate differed between the cell lines. Furthermore, iron supplementation was found to enhance ascorbate-induced cytotoxicity.…”