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Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells

BACKGROUND/AIMS: One of the most important metabolic hallmarks of breast cancer cells is enhanced lipogenesis. Increasing evidences suggest that fatty acid synthase (FAS) plays an important role in human breast cancer. Previously we discovered that alpha-mangostin showed apoptotic effect on human br...

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Autores principales: Huang, Wenyuan, Liang, Yan, Ma, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544980/
https://www.ncbi.nlm.nih.gov/pubmed/31164796
http://dx.doi.org/10.1186/s12935-019-0869-z
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author Huang, Wenyuan
Liang, Yan
Ma, Xiaofeng
author_facet Huang, Wenyuan
Liang, Yan
Ma, Xiaofeng
author_sort Huang, Wenyuan
collection PubMed
description BACKGROUND/AIMS: One of the most important metabolic hallmarks of breast cancer cells is enhanced lipogenesis. Increasing evidences suggest that fatty acid synthase (FAS) plays an important role in human breast cancer. Previously we discovered that alpha-mangostin showed apoptotic effect on human breast cancer cells via inhibiting FAS activity. The endoplasmic reticulum (ER) stress and autophagy are involved in cell apoptosis. However, the role of ER stress and autophagy in FAS inhibition induced apoptosis still remains unclear. METHODS: We evaluated the effects of alpha-mangostin on ER stress and autophagy in human breast cancer cells. Intracellular FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Cell Counting Kit assay was used to test the cell viability. Immunoblot analysis was performed to detect protein expression levels. Apoptotic effects were detected by flow cytometry. RESULTS: Alpha-mangostin induced endoplasmic reticulum stress and autophagy, both of which reduced the apoptotic effect of alpha-mangostin in MDA-MB-231 cells. Palmitic acid, the end product of FAS catalyzed reaction, rescued the ER stress and autophagy induced by alpha-mangostin. Cell apoptosis was markedly promoted by inhibiting ER stress and autophagy while treating cells with alpha-mangostin. CONCLUSION: We propose a hypothesis that a combination of FAS inhibition and ER stress and autophagy inhibition has an application potential in the chemoprevention and treatment of breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0869-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-65449802019-06-04 Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells Huang, Wenyuan Liang, Yan Ma, Xiaofeng Cancer Cell Int Primary Research BACKGROUND/AIMS: One of the most important metabolic hallmarks of breast cancer cells is enhanced lipogenesis. Increasing evidences suggest that fatty acid synthase (FAS) plays an important role in human breast cancer. Previously we discovered that alpha-mangostin showed apoptotic effect on human breast cancer cells via inhibiting FAS activity. The endoplasmic reticulum (ER) stress and autophagy are involved in cell apoptosis. However, the role of ER stress and autophagy in FAS inhibition induced apoptosis still remains unclear. METHODS: We evaluated the effects of alpha-mangostin on ER stress and autophagy in human breast cancer cells. Intracellular FAS activity was measured by a spectrophotometer at 340 nm of NADPH absorption. Cell Counting Kit assay was used to test the cell viability. Immunoblot analysis was performed to detect protein expression levels. Apoptotic effects were detected by flow cytometry. RESULTS: Alpha-mangostin induced endoplasmic reticulum stress and autophagy, both of which reduced the apoptotic effect of alpha-mangostin in MDA-MB-231 cells. Palmitic acid, the end product of FAS catalyzed reaction, rescued the ER stress and autophagy induced by alpha-mangostin. Cell apoptosis was markedly promoted by inhibiting ER stress and autophagy while treating cells with alpha-mangostin. CONCLUSION: We propose a hypothesis that a combination of FAS inhibition and ER stress and autophagy inhibition has an application potential in the chemoprevention and treatment of breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0869-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-31 /pmc/articles/PMC6544980/ /pubmed/31164796 http://dx.doi.org/10.1186/s12935-019-0869-z Text en © The Author(s) 2019 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 Primary Research
Huang, Wenyuan
Liang, Yan
Ma, Xiaofeng
Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells
title Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells
title_full Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells
title_fullStr Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells
title_full_unstemmed Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells
title_short Alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells
title_sort alpha-mangostin induces endoplasmic reticulum stress and autophagy which count against fatty acid synthase inhibition mediated apoptosis in human breast cancer cells
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544980/
https://www.ncbi.nlm.nih.gov/pubmed/31164796
http://dx.doi.org/10.1186/s12935-019-0869-z
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AT maxiaofeng alphamangostininducesendoplasmicreticulumstressandautophagywhichcountagainstfattyacidsynthaseinhibitionmediatedapoptosisinhumanbreastcancercells