ascorbic-acid and Thyroid-Carcinoma--Anaplastic

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.

Topics: Antineoplastic Agents; Ascorbic Acid; Autophagy; Carcinogenesis; Cell Proliferation; Ferritins; Ferroptosis; Humans; Lipid Peroxidation; Oxidative Stress; Phospholipid Hydroperoxide Glutathione Peroxidase; Reactive Oxygen Species; Thyroid Carcinoma, Anaplastic

Anaplastic thyroid carcinoma (ATC) requires more innovative approaches as the current regimes for therapy are inadequate, also most anticancer drugs cause general suppression of physiological functions. However, therapy with limited nontarget tissue damage is desirable. In the present study, we show prooxidant ability of ascorbic acid, which enhances cytotoxicity induced by juglone. We decipher that juglone-ascorbate combination induces reactive oxygen species-mediated apoptosis leading to cell death in ARO cell line originated from ATC. This combination also affects enzyme activity of catalase, glutathione reductase, and superoxide dismutase destabilizing redox balance in cell and thereby making juglone effective at a lower dose. We also show that juglone-ascorbate combination suppresses cell migration, invasion, and expression of tumor-promoting, and angiogenic genes in ARO cell line, thereby disrupting epithelial-mesenchymal transition ability of the cells. Overall, we show that ascorbic acid increases cytotoxic potency of juglone through redox cycling when used in synergy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Cell Movement; Drug Resistance, Neoplasm; Drug Synergism; Gene Expression Regulation, Neoplastic; Glutathione; Humans; Inhibitory Concentration 50; Naphthoquinones; Neoplasm Invasiveness; Neoplasm Proteins; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxidoreductases; RNA Interference; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms