High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 1918
• Main Authors: Choi, Jung-A, Lee, Elizabeth Hyeji, Cho, Hanbyoul, Kim, Jae-Hoon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.01.2023; MDPI
• Subjects: Animals; Antioxidants; Apoptosis; Autophagy; Cancer therapies; Cell Death; Cell growth; Cell proliferation; Cytotoxicity; Depletion; Drug dosages; Female; Ferroptosis; Glutathione peroxidase; Glutathione Peroxidase - metabolism; GPx4; Humans; Lipid peroxidation; Lipids; Medical prognosis; Mice; Mortality; Ovarian cancer; Ovarian Neoplasms - drug therapy; Peroxidase; Selenium; Selenium - metabolism; Selenium - pharmacology; Selenoproteins; Sodium Selenite - metabolism; Sodium Selenite - pharmacology; Tumors; ferroptosis; GPx4; selenium; ovarian cancer; lipid peroxidation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24031918

Selenium is a promising multi-target chemotherapeutic agent with controversial clinical results. Hence, reassessing the anticancer effects of Se is necessary to clearly understand the potential of high-dose selenium in cancer treatment. Here, we observed that high-dose sodium selenite (SS) significantly decreased the proliferation and increased the death of ovarian cancer cells, mediated by an increased generation of reactive oxygen species. Notably, high-dose SS decreased the levels of glutathione peroxidase (GPx), a selenoprotein with antioxidant properties, without altering other selenoproteins. Furthermore, high-dose SS triggered lipid peroxidation and ferroptosis, a type of iron-dependent cell death, due to dysregulated GPx4 pathways. We demonstrated that intravenous high-dose SS significantly reduced the tumor growth and weight in SKOV3-bearing mice. Consistent with our in vitro results, mice with SKOV3 cells treated with high-dose SS showed decreased GPx4 expression in tumors. Therefore, we highlight the significance of high-dose SS as a potential chemotherapeutic agent for ovarian cancer. High-dose SS-mediated ferroptotic therapy integrating glutathione depletion and ROS generation is a promising strategy for cancer therapy.