Vitamin C induces ferroptosis in anaplastic thyroid cancer cells by ferritinophagy activation

Biochem Biophys Res Commun. 2021 Apr 30:551:46-53. doi: 10.1016/j.bbrc.2021.02.126. Epub 2021 Mar 11.


Anaplastic thyroid cancer (ATC) is a rare but highly lethal disease. So far, there is no available established treatment which can prolong its survival. In this regard, effective therapies are urgently needed. Vitamin C widely serves as an anti-cancer agent. However, the potential effects of vitamin C against thyroid tumorigenesis remained unclear. The present study demonstrated that vitamin C could significantly inhibit ATC cells growth through ferroptosis activation, evidenced by the GPX4 inactivation, ROS accumulation and iron-dependent lipid peroxidation. Our results demonstrated that vitamin C treatment induced ferritinophagy and subsequent degradation of ferritin, leading to the release of free iron. Excessive iron further triggered ROS generation via Fenton reaction. The positive feedback mediated by ROS and iron sustained lipid peroxidation and further resulted in ferroptosis of ATC cells. The better understanding of the anti-cancer mechanisms of vitamin C provides a potential strategy for ATC therapy.

Keywords: Anaplastic thyroid cancer; Ferritinophagy; Ferroptosis; Reactive oxygen species; Vitamin C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Ascorbic Acid / pharmacology*
  • Ascorbic Acid / therapeutic use
  • Autophagy / drug effects*
  • Carcinogenesis / drug effects
  • Cell Proliferation / drug effects
  • Ferritins / metabolism*
  • Ferroptosis / drug effects*
  • Humans
  • Lipid Peroxidation
  • Oxidative Stress
  • Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism
  • Reactive Oxygen Species / metabolism
  • Thyroid Carcinoma, Anaplastic / drug therapy
  • Thyroid Carcinoma, Anaplastic / metabolism
  • Thyroid Carcinoma, Anaplastic / pathology*


  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Ferritins
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Ascorbic Acid