Cargando…

High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer

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) significa...

Descripción completa

Detalles Bibliográficos
Autores principales: Choi, Jung-A, Lee, Elizabeth Hyeji, Cho, Hanbyoul, Kim, Jae-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915545/
https://www.ncbi.nlm.nih.gov/pubmed/36768241
http://dx.doi.org/10.3390/ijms24031918
_version_ 1784885925147312128
author Choi, Jung-A
Lee, Elizabeth Hyeji
Cho, Hanbyoul
Kim, Jae-Hoon
author_facet Choi, Jung-A
Lee, Elizabeth Hyeji
Cho, Hanbyoul
Kim, Jae-Hoon
author_sort Choi, Jung-A
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9915545
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99155452023-02-11 High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer Choi, Jung-A Lee, Elizabeth Hyeji Cho, Hanbyoul Kim, Jae-Hoon Int J Mol Sci Article 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. MDPI 2023-01-18 /pmc/articles/PMC9915545/ /pubmed/36768241 http://dx.doi.org/10.3390/ijms24031918 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, Jung-A
Lee, Elizabeth Hyeji
Cho, Hanbyoul
Kim, Jae-Hoon
High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
title High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
title_full High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
title_fullStr High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
title_full_unstemmed High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
title_short High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer
title_sort high-dose selenium induces ferroptotic cell death in ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915545/
https://www.ncbi.nlm.nih.gov/pubmed/36768241
http://dx.doi.org/10.3390/ijms24031918
work_keys_str_mv AT choijunga highdoseseleniuminducesferroptoticcelldeathinovariancancer
AT leeelizabethhyeji highdoseseleniuminducesferroptoticcelldeathinovariancancer
AT chohanbyoul highdoseseleniuminducesferroptoticcelldeathinovariancancer
AT kimjaehoon highdoseseleniuminducesferroptoticcelldeathinovariancancer