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Published on: March 15, 2024
High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
Jung-A Choi1, Elizabeth Hyeji Lee1, Hanbyoul Cho1
1Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Abstract:
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.
Insights
High-dose sodium selenite effectively combats ovarian cancer by increasing cell death and reducing tumor growth. This selenium compound induces ferroptosis, a novel cell death pathway, offering a promising cancer therapy strategy.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Selenium compounds show potential as chemotherapeutics, but clinical results are mixed.
- Re-evaluation of high-dose selenium's anticancer effects is crucial for understanding its therapeutic potential.
Purpose of the Study:
- To investigate the anticancer effects of high-dose sodium selenite (SS) in ovarian cancer.
- To elucidate the mechanisms underlying SS-induced cancer cell death, including reactive oxygen species (ROS) generation and ferroptosis.
Main Methods:
- In vitro studies on ovarian cancer cells treated with high-dose SS.
- Assessment of cell proliferation, cell death, ROS generation, glutathione peroxidase (GPx) levels, and lipid peroxidation.
- In vivo studies using SKOV3-bearing mice treated with intravenous high-dose SS.
- Analysis of tumor growth, tumor weight, and GPx4 expression in tumors.
Main Results:
- High-dose SS significantly inhibited ovarian cancer cell proliferation and induced cell death via increased ROS generation.
- High-dose SS decreased GPx levels, dysregulated GPx4 pathways, and triggered lipid peroxidation and ferroptosis.
- In vivo, high-dose SS administration reduced tumor growth and weight in mice, with decreased GPx4 expression in tumors.
Conclusions:
- High-dose sodium selenite demonstrates significant anticancer efficacy in ovarian cancer models.
- SS-induced ferroptosis, mediated by glutathione depletion and ROS generation, represents a viable therapeutic strategy.
- Further research into high-dose SS warrants its consideration as a chemotherapeutic agent for ovarian cancer.
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