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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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