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Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death

Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-...

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Autores principales: Rodríguez, Juan P., Guijas, Carlos, Astudillo, Alma M., Rubio, Julio M., Balboa, María A., Balsinde, Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521239/
https://www.ncbi.nlm.nih.gov/pubmed/31013768
http://dx.doi.org/10.3390/cancers11040524
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author Rodríguez, Juan P.
Guijas, Carlos
Astudillo, Alma M.
Rubio, Julio M.
Balboa, María A.
Balsinde, Jesús
author_facet Rodríguez, Juan P.
Guijas, Carlos
Astudillo, Alma M.
Rubio, Julio M.
Balboa, María A.
Balsinde, Jesús
author_sort Rodríguez, Juan P.
collection PubMed
description Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-HSA levels in human colorectal tumors are diminished when compared with normal adjacent tissue. Since this decrease could be compatible with an escape mechanism of tumors from 9-HSA-induced apoptosis, we investigated different features of the utilization of this hydroxyfatty acid in colon. We show that in colorectal tumors and related cell lines such as HT-29 and HCT-116, 9-HSA is the only hydroxyfatty acid constituent of branched fatty acid esters of hydroxyfatty acids (FAHFA), a novel family of lipids with anti-inflammatory properties. Importantly, FAHFA levels in tumors are elevated compared with normal tissue and, unlike 9-HSA, they do not induce apoptosis of colorectal cell lines over a wide range of concentrations. Further, the addition of 9-HSA to colon cancer cell lines augments the synthesis of different FAHFA before the cells commit to apoptosis, suggesting that FAHFA formation may function as a buffer system that sequesters the hydroxyacid into an inactive form, thereby restricting apoptosis.
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spelling pubmed-65212392019-05-31 Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death Rodríguez, Juan P. Guijas, Carlos Astudillo, Alma M. Rubio, Julio M. Balboa, María A. Balsinde, Jesús Cancers (Basel) Article Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-HSA levels in human colorectal tumors are diminished when compared with normal adjacent tissue. Since this decrease could be compatible with an escape mechanism of tumors from 9-HSA-induced apoptosis, we investigated different features of the utilization of this hydroxyfatty acid in colon. We show that in colorectal tumors and related cell lines such as HT-29 and HCT-116, 9-HSA is the only hydroxyfatty acid constituent of branched fatty acid esters of hydroxyfatty acids (FAHFA), a novel family of lipids with anti-inflammatory properties. Importantly, FAHFA levels in tumors are elevated compared with normal tissue and, unlike 9-HSA, they do not induce apoptosis of colorectal cell lines over a wide range of concentrations. Further, the addition of 9-HSA to colon cancer cell lines augments the synthesis of different FAHFA before the cells commit to apoptosis, suggesting that FAHFA formation may function as a buffer system that sequesters the hydroxyacid into an inactive form, thereby restricting apoptosis. MDPI 2019-04-12 /pmc/articles/PMC6521239/ /pubmed/31013768 http://dx.doi.org/10.3390/cancers11040524 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rodríguez, Juan P.
Guijas, Carlos
Astudillo, Alma M.
Rubio, Julio M.
Balboa, María A.
Balsinde, Jesús
Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
title Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
title_full Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
title_fullStr Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
title_full_unstemmed Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
title_short Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
title_sort sequestration of 9-hydroxystearic acid in fahfa (fatty acid esters of hydroxy fatty acids) as a protective mechanism for colon carcinoma cells to avoid apoptotic cell death
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521239/
https://www.ncbi.nlm.nih.gov/pubmed/31013768
http://dx.doi.org/10.3390/cancers11040524
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