Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells
Accumulating evidence demonstrated that alteronol, a novel compound that has a similar structure with paclitaxel, exerts anticancer effects against diversified tumors. However, whether alteronol induces autophagy and the relationship between its anticancer effects and autophagy in melanoma remains e...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138813/ https://www.ncbi.nlm.nih.gov/pubmed/32265437 http://dx.doi.org/10.1038/s41419-020-2419-y |
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author | Bao, Yong Ding, Zhi Zhao, Peng Li, Jun Chen, Ping Zheng, Jie Qian, Zhongming |
author_facet | Bao, Yong Ding, Zhi Zhao, Peng Li, Jun Chen, Ping Zheng, Jie Qian, Zhongming |
author_sort | Bao, Yong |
collection | PubMed |
description | Accumulating evidence demonstrated that alteronol, a novel compound that has a similar structure with paclitaxel, exerts anticancer effects against diversified tumors. However, whether alteronol induces autophagy and the relationship between its anticancer effects and autophagy in melanoma remains elusive. In this study, we show that alteronol induces not only anti-proliferation activity and apoptosis but also autophagy in A375 and UACC62 cells. In addition, alteronol inhibits A375 and UACC62 cells invasion and migration by preventing the epithelial–mesenchymal transition (EMT). Blocking autophagy enhances alteronol-induced apoptosis and anti-EMT effects in vitro and in vivo. Mechanistically, we find that alteronol significantly inhibits Akt/mTOR and TGFβ/Smad3 pathways, and co-treatment with autophagy inhibitor 3-MA further potentiate these effects. Our results suggest that alteronol induces cyto-protective autophagy in melanoma cells through inhibition of Akt/mTOR pathway, thus attenuates apoptosis and promotes melanoma cell EMT through TGF-β/Smad3 pathway. Combination with alteronol and autophagy inhibitor 3-MA may be a potential treatment for melanoma as it not only significantly inhibited tumor growth but also suppressed tumor invasion and migration as anti-metastasis agent. |
format | Online Article Text |
id | pubmed-7138813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71388132020-04-08 Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells Bao, Yong Ding, Zhi Zhao, Peng Li, Jun Chen, Ping Zheng, Jie Qian, Zhongming Cell Death Dis Article Accumulating evidence demonstrated that alteronol, a novel compound that has a similar structure with paclitaxel, exerts anticancer effects against diversified tumors. However, whether alteronol induces autophagy and the relationship between its anticancer effects and autophagy in melanoma remains elusive. In this study, we show that alteronol induces not only anti-proliferation activity and apoptosis but also autophagy in A375 and UACC62 cells. In addition, alteronol inhibits A375 and UACC62 cells invasion and migration by preventing the epithelial–mesenchymal transition (EMT). Blocking autophagy enhances alteronol-induced apoptosis and anti-EMT effects in vitro and in vivo. Mechanistically, we find that alteronol significantly inhibits Akt/mTOR and TGFβ/Smad3 pathways, and co-treatment with autophagy inhibitor 3-MA further potentiate these effects. Our results suggest that alteronol induces cyto-protective autophagy in melanoma cells through inhibition of Akt/mTOR pathway, thus attenuates apoptosis and promotes melanoma cell EMT through TGF-β/Smad3 pathway. Combination with alteronol and autophagy inhibitor 3-MA may be a potential treatment for melanoma as it not only significantly inhibited tumor growth but also suppressed tumor invasion and migration as anti-metastasis agent. Nature Publishing Group UK 2020-04-07 /pmc/articles/PMC7138813/ /pubmed/32265437 http://dx.doi.org/10.1038/s41419-020-2419-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Bao, Yong Ding, Zhi Zhao, Peng Li, Jun Chen, Ping Zheng, Jie Qian, Zhongming Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells |
title | Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells |
title_full | Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells |
title_fullStr | Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells |
title_full_unstemmed | Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells |
title_short | Autophagy inhibition potentiates the anti-EMT effects of alteronol through TGF-β/Smad3 signaling in melanoma cells |
title_sort | autophagy inhibition potentiates the anti-emt effects of alteronol through tgf-β/smad3 signaling in melanoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138813/ https://www.ncbi.nlm.nih.gov/pubmed/32265437 http://dx.doi.org/10.1038/s41419-020-2419-y |
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