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Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer
Microtubules are one of the major targets for anticancer drugs because of their role in cell proliferation and migration. However, as anticancer drugs targeting microtubules have side effects, including the death of normal cells, it is necessary to develop anticancer agents that can target microtubu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555225/ https://www.ncbi.nlm.nih.gov/pubmed/32917017 http://dx.doi.org/10.3390/biomedicines8090338 |
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author | Kwon, Ahreum Lee, Gwi Bin Park, Taein Lee, Jung Hoon Ko, Panseon You, Eunae Ahn, Jin Hee Eom, Soo Hyun Rhee, Sangmyung Song, Woo Keun |
author_facet | Kwon, Ahreum Lee, Gwi Bin Park, Taein Lee, Jung Hoon Ko, Panseon You, Eunae Ahn, Jin Hee Eom, Soo Hyun Rhee, Sangmyung Song, Woo Keun |
author_sort | Kwon, Ahreum |
collection | PubMed |
description | Microtubules are one of the major targets for anticancer drugs because of their role in cell proliferation and migration. However, as anticancer drugs targeting microtubules have side effects, including the death of normal cells, it is necessary to develop anticancer agents that can target microtubules by specifically acting on cancer cells only. In this study, we identified chemicals that can act as anticancer agents by specifically binding to acetylated microtubules, which are predominant in triple-negative breast cancer (TNBC). The chemical compounds disrupted acetylated microtubule lattices by interfering with microtubule access to alpha-tubulin acetyltransferase 1 (αTAT1), a major acetyltransferase of microtubules, resulting in the increased apoptotic cell death of MDA-MB-231 cells (a TNBC cell line) compared with other cells, such as MCF-10A and MCF-7, which lack microtubule acetylation. Moreover, mouse xenograft experiments showed that treatment with the chemical compounds markedly reduced tumor growth progression. Taken together, the newly identified chemical compounds can be selective for acetylated microtubules and act as potential therapeutic agents against microtubule acetylation enrichment in TNBC. |
format | Online Article Text |
id | pubmed-7555225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75552252020-10-19 Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer Kwon, Ahreum Lee, Gwi Bin Park, Taein Lee, Jung Hoon Ko, Panseon You, Eunae Ahn, Jin Hee Eom, Soo Hyun Rhee, Sangmyung Song, Woo Keun Biomedicines Article Microtubules are one of the major targets for anticancer drugs because of their role in cell proliferation and migration. However, as anticancer drugs targeting microtubules have side effects, including the death of normal cells, it is necessary to develop anticancer agents that can target microtubules by specifically acting on cancer cells only. In this study, we identified chemicals that can act as anticancer agents by specifically binding to acetylated microtubules, which are predominant in triple-negative breast cancer (TNBC). The chemical compounds disrupted acetylated microtubule lattices by interfering with microtubule access to alpha-tubulin acetyltransferase 1 (αTAT1), a major acetyltransferase of microtubules, resulting in the increased apoptotic cell death of MDA-MB-231 cells (a TNBC cell line) compared with other cells, such as MCF-10A and MCF-7, which lack microtubule acetylation. Moreover, mouse xenograft experiments showed that treatment with the chemical compounds markedly reduced tumor growth progression. Taken together, the newly identified chemical compounds can be selective for acetylated microtubules and act as potential therapeutic agents against microtubule acetylation enrichment in TNBC. MDPI 2020-09-09 /pmc/articles/PMC7555225/ /pubmed/32917017 http://dx.doi.org/10.3390/biomedicines8090338 Text en © 2020 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 Kwon, Ahreum Lee, Gwi Bin Park, Taein Lee, Jung Hoon Ko, Panseon You, Eunae Ahn, Jin Hee Eom, Soo Hyun Rhee, Sangmyung Song, Woo Keun Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer |
title | Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer |
title_full | Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer |
title_fullStr | Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer |
title_full_unstemmed | Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer |
title_short | Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer |
title_sort | potent small-molecule inhibitors targeting acetylated microtubules as anticancer agents against triple-negative breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555225/ https://www.ncbi.nlm.nih.gov/pubmed/32917017 http://dx.doi.org/10.3390/biomedicines8090338 |
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