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Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells

BACKGROUND: Fatty acid synthase (FAS) has been proven over-expressed in human breast cancer cells and consequently, has been recognized as a target for breast cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen pericarp, has a variety of biological activities, including anti-ca...

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Autores principales: Li, Ping, Tian, Weixi, Ma, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060095/
https://www.ncbi.nlm.nih.gov/pubmed/24894151
http://dx.doi.org/10.1186/1476-4598-13-138
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author Li, Ping
Tian, Weixi
Ma, Xiaofeng
author_facet Li, Ping
Tian, Weixi
Ma, Xiaofeng
author_sort Li, Ping
collection PubMed
description BACKGROUND: Fatty acid synthase (FAS) has been proven over-expressed in human breast cancer cells and consequently, has been recognized as a target for breast cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen pericarp, has a variety of biological activities, including anti-cancer effect. In our previous study, alpha-mangostin had been found both fast-binding and slow-binding inhibitions to FAS in vitro. This study was designed to investigate the activity of alpha-mangostin on intracellular FAS activity in FAS over-expressed human breast cancer cells, and to testify whether the anti-cancer activity of alpha-mangostin may be related to its inhibitory effect on FAS. METHODS: We evaluated the cytotoxicity of alpha-mangostin in human breast cancer MCF-7 and MDA-MB-231 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 FAS expression level, intracellular fatty acid accumulation and cell signaling (FAK, ERK1/2 and AKT). Apoptotic effects were detected by flow cytometry and immunoblot analysis of PARP, Bax and Bcl-2. Small interfering RNA was used to down-regulate FAS expression and/or activity. RESULTS: Alpha-mangostin could effectively suppress FAS expression and inhibit intracellular FAS activity, and result in decrease of intracellular fatty acid accumulation. It could also reduce cell viability, induce apoptosis in human breast cancer cells, increase in the levels of the PARP cleavage product, and attenuate the balance between anti-apoptotic and pro-apoptotic proteins of the Bcl-2 family. Moreover, alpha-mangostin inhibited the phosphorylation of FAK. However, the active forms of AKT, and ERK1/2 proteins were not involved in the changes of FAS expression induced by alpha-mangostin. CONCLUSIONS: Alpha-mangostin induced breast cancer cell apoptosis by inhibiting FAS, which provide a basis for the development of xanthone as an agent for breast cancer therapy.
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spelling pubmed-40600952014-06-18 Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells Li, Ping Tian, Weixi Ma, Xiaofeng Mol Cancer Research BACKGROUND: Fatty acid synthase (FAS) has been proven over-expressed in human breast cancer cells and consequently, has been recognized as a target for breast cancer treatment. Alpha-mangostin, a natural xanthone found in mangosteen pericarp, has a variety of biological activities, including anti-cancer effect. In our previous study, alpha-mangostin had been found both fast-binding and slow-binding inhibitions to FAS in vitro. This study was designed to investigate the activity of alpha-mangostin on intracellular FAS activity in FAS over-expressed human breast cancer cells, and to testify whether the anti-cancer activity of alpha-mangostin may be related to its inhibitory effect on FAS. METHODS: We evaluated the cytotoxicity of alpha-mangostin in human breast cancer MCF-7 and MDA-MB-231 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 FAS expression level, intracellular fatty acid accumulation and cell signaling (FAK, ERK1/2 and AKT). Apoptotic effects were detected by flow cytometry and immunoblot analysis of PARP, Bax and Bcl-2. Small interfering RNA was used to down-regulate FAS expression and/or activity. RESULTS: Alpha-mangostin could effectively suppress FAS expression and inhibit intracellular FAS activity, and result in decrease of intracellular fatty acid accumulation. It could also reduce cell viability, induce apoptosis in human breast cancer cells, increase in the levels of the PARP cleavage product, and attenuate the balance between anti-apoptotic and pro-apoptotic proteins of the Bcl-2 family. Moreover, alpha-mangostin inhibited the phosphorylation of FAK. However, the active forms of AKT, and ERK1/2 proteins were not involved in the changes of FAS expression induced by alpha-mangostin. CONCLUSIONS: Alpha-mangostin induced breast cancer cell apoptosis by inhibiting FAS, which provide a basis for the development of xanthone as an agent for breast cancer therapy. BioMed Central 2014-06-03 /pmc/articles/PMC4060095/ /pubmed/24894151 http://dx.doi.org/10.1186/1476-4598-13-138 Text en Copyright © 2014 Li et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
Li, Ping
Tian, Weixi
Ma, Xiaofeng
Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells
title Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells
title_full Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells
title_fullStr Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells
title_full_unstemmed Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells
title_short Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells
title_sort alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060095/
https://www.ncbi.nlm.nih.gov/pubmed/24894151
http://dx.doi.org/10.1186/1476-4598-13-138
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AT maxiaofeng alphamangostininhibitsintracellularfattyacidsynthaseandinducesapoptosisinbreastcancercells