High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
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| Název: | High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer |
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| Přispěvatelé: | Jung-A Choi, Elizabeth Hyeji Lee, Hanbyoul Cho, Jae-Hoon Kim, Kim, Jae Hoon |
| Informace o vydavateli: | MDPI |
| Rok vydání: | 2023 |
| Témata: | Animals, Cell Death, Female, Glutathione Peroxidase / metabolism, Humans, Mice, Ovarian Neoplasms* / drug therapy, Selenium* / metabolism, Selenium* / pharmacology, Selenoproteins, Sodium Selenite / metabolism, Sodium Selenite / pharmacology, GPx4, ferroptosis, lipid peroxidation, ovarian cancer, selenium |
| Popis: | 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. ; open |
| Druh dokumentu: | article in journal/newspaper |
| Jazyk: | English |
| Relation: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; J01133; https://ir.ymlib.yonsei.ac.kr/handle/22282913/193714; T202301623 |
| DOI: | 10.3390/ijms24031918 |
| Dostupnost: | https://ir.ymlib.yonsei.ac.kr/handle/22282913/193714 https://doi.org/10.3390/ijms24031918 |
| Rights: | CC BY-NC-ND 2.0 KR |
| Přístupové číslo: | edsbas.FC09036A |
| Databáze: | BASE |
Nájsť tento článok vo Web of Science | Abstrakt: | 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. ; open |
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| DOI: | 10.3390/ijms24031918 |