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Resveratrol induces autophagy-dependent apoptosis in HL-60 cells
BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-re...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964919/ https://www.ncbi.nlm.nih.gov/pubmed/29788929 http://dx.doi.org/10.1186/s12885-018-4504-5 |
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author | Fan, Yingying Chiu, Jen-Fu Liu, Jing Deng, Yan Xu, Cheng Zhang, Jun Li, Guanwu |
author_facet | Fan, Yingying Chiu, Jen-Fu Liu, Jing Deng, Yan Xu, Cheng Zhang, Jun Li, Guanwu |
author_sort | Fan, Yingying |
collection | PubMed |
description | BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student’s unpaired t test. RESULTS: We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. CONCLUSIONS: These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4504-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5964919 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59649192018-05-24 Resveratrol induces autophagy-dependent apoptosis in HL-60 cells Fan, Yingying Chiu, Jen-Fu Liu, Jing Deng, Yan Xu, Cheng Zhang, Jun Li, Guanwu BMC Cancer Research Article BACKGROUND: All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS: Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student’s unpaired t test. RESULTS: We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. CONCLUSIONS: These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4504-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-22 /pmc/articles/PMC5964919/ /pubmed/29788929 http://dx.doi.org/10.1186/s12885-018-4504-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Fan, Yingying Chiu, Jen-Fu Liu, Jing Deng, Yan Xu, Cheng Zhang, Jun Li, Guanwu Resveratrol induces autophagy-dependent apoptosis in HL-60 cells |
title | Resveratrol induces autophagy-dependent apoptosis in HL-60 cells |
title_full | Resveratrol induces autophagy-dependent apoptosis in HL-60 cells |
title_fullStr | Resveratrol induces autophagy-dependent apoptosis in HL-60 cells |
title_full_unstemmed | Resveratrol induces autophagy-dependent apoptosis in HL-60 cells |
title_short | Resveratrol induces autophagy-dependent apoptosis in HL-60 cells |
title_sort | resveratrol induces autophagy-dependent apoptosis in hl-60 cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964919/ https://www.ncbi.nlm.nih.gov/pubmed/29788929 http://dx.doi.org/10.1186/s12885-018-4504-5 |
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