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RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer
Cancer-derived small extracellular vesicles (sEVs) serve as critical mediators of cell-to-cell communication. Manzamine A (MA), a unique marine-derived alkaloid with various bioactivities, exerts anticancer effects against several kinds of tumors, but it remains unclear whether it has the same activ...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051755/ https://www.ncbi.nlm.nih.gov/pubmed/36976201 http://dx.doi.org/10.3390/md21030151 |
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author | Wang, Xuan Liu, Yuanpeng Qin, Huan Qi, Guocui Chen, Xuehong Lyu, Yi Han, Yantao |
author_facet | Wang, Xuan Liu, Yuanpeng Qin, Huan Qi, Guocui Chen, Xuehong Lyu, Yi Han, Yantao |
author_sort | Wang, Xuan |
collection | PubMed |
description | Cancer-derived small extracellular vesicles (sEVs) serve as critical mediators of cell-to-cell communication. Manzamine A (MA), a unique marine-derived alkaloid with various bioactivities, exerts anticancer effects against several kinds of tumors, but it remains unclear whether it has the same activity against breast cancer. Here, we proved that MA inhibits MDA-MB-231 and MCF-7 cell proliferation, migration, and invasion in a time- and dose-dependent manner. In addition, MA promotes autophagosome formation but suppresses autophagosome degradation in breast cancer cells. Importantly, we also found that MA stimulates sEVs secretion and increases autophagy-related protein accumulation in secreted sEVs, further potentiated by autophagy inhibitor chloroquine (CQ). Mechanistically, MA decreases the expression level of RIP1, the key upstream regulator of the autophagic pathway, and reduces the acidity of lysosome. Overexpression of RIP1 activated AKT/mTOR signaling, thus attenuating MA-induced autophagy and the corresponding secretion of autophagy-associated sEVs. Collectively, these data suggested that MA is a potential inhibitor of autophagy by preventing autophagosome turnover, and RIP1 mediates MA-induced secretory autophagy, which may be efficacious for breast cancer treatment. |
format | Online Article Text |
id | pubmed-10051755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100517552023-03-30 RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer Wang, Xuan Liu, Yuanpeng Qin, Huan Qi, Guocui Chen, Xuehong Lyu, Yi Han, Yantao Mar Drugs Article Cancer-derived small extracellular vesicles (sEVs) serve as critical mediators of cell-to-cell communication. Manzamine A (MA), a unique marine-derived alkaloid with various bioactivities, exerts anticancer effects against several kinds of tumors, but it remains unclear whether it has the same activity against breast cancer. Here, we proved that MA inhibits MDA-MB-231 and MCF-7 cell proliferation, migration, and invasion in a time- and dose-dependent manner. In addition, MA promotes autophagosome formation but suppresses autophagosome degradation in breast cancer cells. Importantly, we also found that MA stimulates sEVs secretion and increases autophagy-related protein accumulation in secreted sEVs, further potentiated by autophagy inhibitor chloroquine (CQ). Mechanistically, MA decreases the expression level of RIP1, the key upstream regulator of the autophagic pathway, and reduces the acidity of lysosome. Overexpression of RIP1 activated AKT/mTOR signaling, thus attenuating MA-induced autophagy and the corresponding secretion of autophagy-associated sEVs. Collectively, these data suggested that MA is a potential inhibitor of autophagy by preventing autophagosome turnover, and RIP1 mediates MA-induced secretory autophagy, which may be efficacious for breast cancer treatment. MDPI 2023-02-25 /pmc/articles/PMC10051755/ /pubmed/36976201 http://dx.doi.org/10.3390/md21030151 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Xuan Liu, Yuanpeng Qin, Huan Qi, Guocui Chen, Xuehong Lyu, Yi Han, Yantao RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer |
title | RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer |
title_full | RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer |
title_fullStr | RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer |
title_full_unstemmed | RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer |
title_short | RIP1 Mediates Manzamine-A-Induced Secretory Autophagy in Breast Cancer |
title_sort | rip1 mediates manzamine-a-induced secretory autophagy in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051755/ https://www.ncbi.nlm.nih.gov/pubmed/36976201 http://dx.doi.org/10.3390/md21030151 |
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