Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Yong, Shu, Furong, Liang, Xinyu, Chang, Hui, Shi, Linying, Peng, Xiaoli, Zhu, Jundong, Mi, Mantian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782303671990616064
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
work_keys_str_mv AT zhouyong ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway
AT shufurong ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway
AT liangxinyu ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway
AT changhui ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway
AT shilinying ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway
AT pengxiaoli ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway
AT zhujundong ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway
AT mimantian ampelopsininducescellgrowthinhibitionandapoptosisinbreastcancercellsthroughrosgenerationandendoplasmicreticulumstresspathway