Cargando…

Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells

Apoptosis plays a crucial role in maintaining the structural and functional integrity of the intestinal epithelial barrier. Autophagy mediates injury to and repair of the intestinal epithelial barrier through multiple pathways in pathophysiological conditions. Our earlier study has found that cucurb...

Descripción completa

Detalles Bibliográficos
Autores principales: Song, Huapei, Sui, Hehuan, Zhang, Qiong, Wang, Pei, Wang, Fengjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479753/
https://www.ncbi.nlm.nih.gov/pubmed/32982778
http://dx.doi.org/10.3389/fphys.2020.01020
_version_ 1783580321850064896
author Song, Huapei
Sui, Hehuan
Zhang, Qiong
Wang, Pei
Wang, Fengjun
author_facet Song, Huapei
Sui, Hehuan
Zhang, Qiong
Wang, Pei
Wang, Fengjun
author_sort Song, Huapei
collection PubMed
description Apoptosis plays a crucial role in maintaining the structural and functional integrity of the intestinal epithelial barrier. Autophagy mediates injury to and repair of the intestinal epithelial barrier through multiple pathways in pathophysiological conditions. Our earlier study has found that cucurbitacin E (CuE) regulates the proliferation, migration, and permeability of human intestinal epithelial cells (IECs); however, its effects and mechanisms on apoptosis and autophagy are still unclear. This study reported CuE induced apoptosis and promoted autophagy of IECs in a concentration-dependent manner. The results showed that CuE could inhibit the expression of apoptosis-related protein Bcl-2 and drove activation of caspase-3 and cleavage of its substrate poly (ADP-ribose) polymerase. CuE also facilitated the expression of endoplasmic reticulum stress-related proteins, CHOP and Grp78, and autophagy-related proteins, Beclin1 and LC3, while inhibiting the phosphorylation of AKT and mammalian target of rapamycin (mTOR). An autophagy inhibitor, 3-methyladenine, reduced CuE-induced apoptosis. These results suggest that CuE may induce apoptosis and autophagy in IECs via the PI3K/AKT/mTOR signaling pathway and that autophagy following endoplasmic reticulum stress participates in the pro-apoptotic process induced by CuE.
format Online
Article
Text
id pubmed-7479753
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-74797532020-09-24 Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells Song, Huapei Sui, Hehuan Zhang, Qiong Wang, Pei Wang, Fengjun Front Physiol Physiology Apoptosis plays a crucial role in maintaining the structural and functional integrity of the intestinal epithelial barrier. Autophagy mediates injury to and repair of the intestinal epithelial barrier through multiple pathways in pathophysiological conditions. Our earlier study has found that cucurbitacin E (CuE) regulates the proliferation, migration, and permeability of human intestinal epithelial cells (IECs); however, its effects and mechanisms on apoptosis and autophagy are still unclear. This study reported CuE induced apoptosis and promoted autophagy of IECs in a concentration-dependent manner. The results showed that CuE could inhibit the expression of apoptosis-related protein Bcl-2 and drove activation of caspase-3 and cleavage of its substrate poly (ADP-ribose) polymerase. CuE also facilitated the expression of endoplasmic reticulum stress-related proteins, CHOP and Grp78, and autophagy-related proteins, Beclin1 and LC3, while inhibiting the phosphorylation of AKT and mammalian target of rapamycin (mTOR). An autophagy inhibitor, 3-methyladenine, reduced CuE-induced apoptosis. These results suggest that CuE may induce apoptosis and autophagy in IECs via the PI3K/AKT/mTOR signaling pathway and that autophagy following endoplasmic reticulum stress participates in the pro-apoptotic process induced by CuE. Frontiers Media S.A. 2020-08-26 /pmc/articles/PMC7479753/ /pubmed/32982778 http://dx.doi.org/10.3389/fphys.2020.01020 Text en Copyright © 2020 Song, Sui, Zhang, Wang and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Song, Huapei
Sui, Hehuan
Zhang, Qiong
Wang, Pei
Wang, Fengjun
Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells
title Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells
title_full Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells
title_fullStr Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells
title_full_unstemmed Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells
title_short Cucurbitacin E Induces Autophagy-Involved Apoptosis in Intestinal Epithelial Cells
title_sort cucurbitacin e induces autophagy-involved apoptosis in intestinal epithelial cells
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479753/
https://www.ncbi.nlm.nih.gov/pubmed/32982778
http://dx.doi.org/10.3389/fphys.2020.01020
work_keys_str_mv AT songhuapei cucurbitacineinducesautophagyinvolvedapoptosisinintestinalepithelialcells
AT suihehuan cucurbitacineinducesautophagyinvolvedapoptosisinintestinalepithelialcells
AT zhangqiong cucurbitacineinducesautophagyinvolvedapoptosisinintestinalepithelialcells
AT wangpei cucurbitacineinducesautophagyinvolvedapoptosisinintestinalepithelialcells
AT wangfengjun cucurbitacineinducesautophagyinvolvedapoptosisinintestinalepithelialcells