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Selenite Inhibits Notch Signaling in Cells and Mice
Selenium is an essential micronutrient with a wide range of biological effects in mammals. The inorganic form of selenium, selenite, is supplemented to relieve individuals with selenium deficiency and to alleviate associated symptoms. Additionally, physiological and supranutritional selenite have sh...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959125/ https://www.ncbi.nlm.nih.gov/pubmed/33802299 http://dx.doi.org/10.3390/ijms22052518 |
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author | Powers, Michael Liu, Liu Deemer, Dane Chen, Selina Scholl, Aaron Yoshinaga, Masafumi Liu, Zijuan |
author_facet | Powers, Michael Liu, Liu Deemer, Dane Chen, Selina Scholl, Aaron Yoshinaga, Masafumi Liu, Zijuan |
author_sort | Powers, Michael |
collection | PubMed |
description | Selenium is an essential micronutrient with a wide range of biological effects in mammals. The inorganic form of selenium, selenite, is supplemented to relieve individuals with selenium deficiency and to alleviate associated symptoms. Additionally, physiological and supranutritional selenite have shown selectively higher affinity and toxicity towards cancer cells, highlighting their potential to serve as chemotherapeutic agents or adjuvants. At varying doses, selenite extensively regulates cellular signaling and modulates many cellular processes. In this study, we report the identification of Delta–Notch signaling as a previously uncharacterized selenite inhibited target. Our transcriptomic results in selenite treated primary mouse hepatocytes revealed that the transcription of Notch1, Notch2, Hes1, Maml1, Furin and c-Myc were all decreased following selenite treatment. We further showed that selenite can inhibit Notch1 expression in cultured MCF7 breast adenocarcinoma cells and HEPG2 liver carcinoma cells. In mice acutely treated with 2.5 mg/kg selenite via intraperitoneal injection, we found that Notch1 expression was drastically lowered in liver and kidney tissues by 90% and 70%, respectively. Combined, these results support selenite as a novel inhibitor of Notch signaling, and a plausible mechanism of inhibition has been proposed. This discovery highlights the potential value of selenite applied in a pathological context where Notch is a key drug target in diseases such as cancer, fibrosis, and neurodegenerative disorders. |
format | Online Article Text |
id | pubmed-7959125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79591252021-03-16 Selenite Inhibits Notch Signaling in Cells and Mice Powers, Michael Liu, Liu Deemer, Dane Chen, Selina Scholl, Aaron Yoshinaga, Masafumi Liu, Zijuan Int J Mol Sci Article Selenium is an essential micronutrient with a wide range of biological effects in mammals. The inorganic form of selenium, selenite, is supplemented to relieve individuals with selenium deficiency and to alleviate associated symptoms. Additionally, physiological and supranutritional selenite have shown selectively higher affinity and toxicity towards cancer cells, highlighting their potential to serve as chemotherapeutic agents or adjuvants. At varying doses, selenite extensively regulates cellular signaling and modulates many cellular processes. In this study, we report the identification of Delta–Notch signaling as a previously uncharacterized selenite inhibited target. Our transcriptomic results in selenite treated primary mouse hepatocytes revealed that the transcription of Notch1, Notch2, Hes1, Maml1, Furin and c-Myc were all decreased following selenite treatment. We further showed that selenite can inhibit Notch1 expression in cultured MCF7 breast adenocarcinoma cells and HEPG2 liver carcinoma cells. In mice acutely treated with 2.5 mg/kg selenite via intraperitoneal injection, we found that Notch1 expression was drastically lowered in liver and kidney tissues by 90% and 70%, respectively. Combined, these results support selenite as a novel inhibitor of Notch signaling, and a plausible mechanism of inhibition has been proposed. This discovery highlights the potential value of selenite applied in a pathological context where Notch is a key drug target in diseases such as cancer, fibrosis, and neurodegenerative disorders. MDPI 2021-03-03 /pmc/articles/PMC7959125/ /pubmed/33802299 http://dx.doi.org/10.3390/ijms22052518 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Powers, Michael Liu, Liu Deemer, Dane Chen, Selina Scholl, Aaron Yoshinaga, Masafumi Liu, Zijuan Selenite Inhibits Notch Signaling in Cells and Mice |
title | Selenite Inhibits Notch Signaling in Cells and Mice |
title_full | Selenite Inhibits Notch Signaling in Cells and Mice |
title_fullStr | Selenite Inhibits Notch Signaling in Cells and Mice |
title_full_unstemmed | Selenite Inhibits Notch Signaling in Cells and Mice |
title_short | Selenite Inhibits Notch Signaling in Cells and Mice |
title_sort | selenite inhibits notch signaling in cells and mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959125/ https://www.ncbi.nlm.nih.gov/pubmed/33802299 http://dx.doi.org/10.3390/ijms22052518 |
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