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A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis
Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhy...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214212/ https://www.ncbi.nlm.nih.gov/pubmed/37186828 http://dx.doi.org/10.1073/pnas.2304081120 |
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author | Kim, Ji Hyeon Park, Soeun Jung, Eunsun Shin, Jinwoo Kim, Yoon-Jae Kim, Ji Young Sessler, Jonathan L. Seo, Jae Hong Kim, Jong Seung |
author_facet | Kim, Ji Hyeon Park, Soeun Jung, Eunsun Shin, Jinwoo Kim, Yoon-Jae Kim, Ji Young Sessler, Jonathan L. Seo, Jae Hong Kim, Jong Seung |
author_sort | Kim, Ji Hyeon |
collection | PubMed |
description | Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhydrase IX (CAIX) inhibitor, acetazolamide, with a signal transducer and transcriptional activator 3 (STAT3) inhibitor, niclosamide. Nic-A was designed to target triple-negative breast cancer (TNBC) CSCs and was found to inhibit both proliferating TNBC cells and CSCs via STAT3 dysregulation and suppression of CSC-like properties. Its use leads to a decrease in aldehyde dehydrogenase 1 activity, CD44(high)/CD24(low) stem-like subpopulations, and tumor spheroid-forming ability. TNBC xenograft tumors treated with Nic-A exhibited decreased angiogenesis and tumor growth, as well as decreased Ki-67 expression and increased apoptosis. In addition, distant metastases were suppressed in TNBC allografts derived from a CSC-enriched population. This study thus highlights a potential strategy for addressing CSC-based cancer recurrence. |
format | Online Article Text |
id | pubmed-10214212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-102142122023-11-15 A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis Kim, Ji Hyeon Park, Soeun Jung, Eunsun Shin, Jinwoo Kim, Yoon-Jae Kim, Ji Young Sessler, Jonathan L. Seo, Jae Hong Kim, Jong Seung Proc Natl Acad Sci U S A Biological Sciences Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhydrase IX (CAIX) inhibitor, acetazolamide, with a signal transducer and transcriptional activator 3 (STAT3) inhibitor, niclosamide. Nic-A was designed to target triple-negative breast cancer (TNBC) CSCs and was found to inhibit both proliferating TNBC cells and CSCs via STAT3 dysregulation and suppression of CSC-like properties. Its use leads to a decrease in aldehyde dehydrogenase 1 activity, CD44(high)/CD24(low) stem-like subpopulations, and tumor spheroid-forming ability. TNBC xenograft tumors treated with Nic-A exhibited decreased angiogenesis and tumor growth, as well as decreased Ki-67 expression and increased apoptosis. In addition, distant metastases were suppressed in TNBC allografts derived from a CSC-enriched population. This study thus highlights a potential strategy for addressing CSC-based cancer recurrence. National Academy of Sciences 2023-05-15 2023-05-23 /pmc/articles/PMC10214212/ /pubmed/37186828 http://dx.doi.org/10.1073/pnas.2304081120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Kim, Ji Hyeon Park, Soeun Jung, Eunsun Shin, Jinwoo Kim, Yoon-Jae Kim, Ji Young Sessler, Jonathan L. Seo, Jae Hong Kim, Jong Seung A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis |
title | A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis |
title_full | A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis |
title_fullStr | A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis |
title_full_unstemmed | A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis |
title_short | A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis |
title_sort | dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits tnbc metastasis |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214212/ https://www.ncbi.nlm.nih.gov/pubmed/37186828 http://dx.doi.org/10.1073/pnas.2304081120 |
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