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

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. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study demonstrated that vitamin C can significantly inhibit the growth of anaplastic thyroid cancer cells through ferroptosis activation, involving GPX4 inactivation, ROS accumulation, and iron-dependent lipid peroxidation. The mechanism includes induction of ferritinophagy, degradation of ferritin, release of free iron, and subsequent ROS generation via Fenton reaction. This positive feedback loop sustained lipid peroxidation and led to the ferroptosis of ATC cells, providing a potential strategy for ATC therapy.