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Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway
Ampelopsin (AMP), a major bioactive constituent of Ampelopsis grossedentata, exerts a number of biological effects. In this study, we investigated its anti-cancer activity in human breast cancer cell lines, and explored the underlying mechanism of this action. Our results showed that treatment with...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923868/ https://www.ncbi.nlm.nih.gov/pubmed/24551210 http://dx.doi.org/10.1371/journal.pone.0089021 |
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author | Zhou, Yong Shu, Furong Liang, Xinyu Chang, Hui Shi, Linying Peng, Xiaoli Zhu, Jundong Mi, Mantian |
author_facet | Zhou, Yong Shu, Furong Liang, Xinyu Chang, Hui Shi, Linying Peng, Xiaoli Zhu, Jundong Mi, Mantian |
author_sort | Zhou, Yong |
collection | PubMed |
description | Ampelopsin (AMP), a major bioactive constituent of Ampelopsis grossedentata, exerts a number of biological effects. In this study, we investigated its anti-cancer activity in human breast cancer cell lines, and explored the underlying mechanism of this action. Our results showed that treatment with AMP dose-dependently inhibited cell viability and induced apoptosis in MCF-7 and MDA-MB-231 breast cancer cells without cytotoxicity in human normal breast epithelial cells MCF-10A. Meanwhile, AMP dose- dependently triggered reactive oxygen species (ROS) generation in both breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) strongly attenuated AMP-induced ROS production, along with cell growth inhibition and apoptosis. Furthermore, AMP was observed to activate endoplasmic reticulum (ER) stress, as evidenced by the up-regulation of ER stress-related proteins, including GRP78, p-PERK, p-elF2α, cleaved ATF6α and CHOP, while knockdown of ATF6α or PERK markedly down-regulated AMP-induced CHOP expression. Blocking ER stress using 4-phenylbutyric acid not only down-regulated AMP-induced GRP78 and CHOP expression, but also significantly decreased AMP-induced cell growth inhibition and apoptosis, whereas ER stress inducer thapsigargin played opposing effects. Additionally, NAC inhibited AMP-induced ER stress by down-regulating GRP78 and CHOP expression. Conversely, blocking ER stress using CHOP siRNA decreased AMP-induced ROS production and cell apoptosis. Taken together, these results demonstrate that AMP has anti-tumor effects against breast cancer cells through ROS generation and ER stress pathway, which therefore provide experimental evidences for developing AMP as a new therapeutic drug for breast cancer. |
format | Online Article Text |
id | pubmed-3923868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39238682014-02-18 Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway Zhou, Yong Shu, Furong Liang, Xinyu Chang, Hui Shi, Linying Peng, Xiaoli Zhu, Jundong Mi, Mantian PLoS One Research Article Ampelopsin (AMP), a major bioactive constituent of Ampelopsis grossedentata, exerts a number of biological effects. In this study, we investigated its anti-cancer activity in human breast cancer cell lines, and explored the underlying mechanism of this action. Our results showed that treatment with AMP dose-dependently inhibited cell viability and induced apoptosis in MCF-7 and MDA-MB-231 breast cancer cells without cytotoxicity in human normal breast epithelial cells MCF-10A. Meanwhile, AMP dose- dependently triggered reactive oxygen species (ROS) generation in both breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) strongly attenuated AMP-induced ROS production, along with cell growth inhibition and apoptosis. Furthermore, AMP was observed to activate endoplasmic reticulum (ER) stress, as evidenced by the up-regulation of ER stress-related proteins, including GRP78, p-PERK, p-elF2α, cleaved ATF6α and CHOP, while knockdown of ATF6α or PERK markedly down-regulated AMP-induced CHOP expression. Blocking ER stress using 4-phenylbutyric acid not only down-regulated AMP-induced GRP78 and CHOP expression, but also significantly decreased AMP-induced cell growth inhibition and apoptosis, whereas ER stress inducer thapsigargin played opposing effects. Additionally, NAC inhibited AMP-induced ER stress by down-regulating GRP78 and CHOP expression. Conversely, blocking ER stress using CHOP siRNA decreased AMP-induced ROS production and cell apoptosis. Taken together, these results demonstrate that AMP has anti-tumor effects against breast cancer cells through ROS generation and ER stress pathway, which therefore provide experimental evidences for developing AMP as a new therapeutic drug for breast cancer. Public Library of Science 2014-02-13 /pmc/articles/PMC3923868/ /pubmed/24551210 http://dx.doi.org/10.1371/journal.pone.0089021 Text en © 2014 Zhou et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhou, Yong Shu, Furong Liang, Xinyu Chang, Hui Shi, Linying Peng, Xiaoli Zhu, Jundong Mi, Mantian Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway |
title | Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway |
title_full | Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway |
title_fullStr | Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway |
title_full_unstemmed | Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway |
title_short | Ampelopsin Induces Cell Growth Inhibition and Apoptosis in Breast Cancer Cells through ROS Generation and Endoplasmic Reticulum Stress Pathway |
title_sort | ampelopsin induces cell growth inhibition and apoptosis in breast cancer cells through ros generation and endoplasmic reticulum stress pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923868/ https://www.ncbi.nlm.nih.gov/pubmed/24551210 http://dx.doi.org/10.1371/journal.pone.0089021 |
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