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

Autor: Juan Pablo Rodríguez, Alma M. Astudillo, Julio M. Rubio, Jesús Balsinde, María A. Balboa, Carlos Guijas
Přispěvatelé: Consejo Superior de Investigaciones Científicas (España), Ministerio de Economía y Competitividad (España), Universidad de Valladolid, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (España), CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI)
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
Cell cycle checkpoint
Colorectal cancer
colorectal cancer
lcsh:RC254-282
Article
purl.org/becyt/ford/1 [https]
Ácido hidroxiesteárico
Ciencias Biológicas
03 medical and health sciences
0302 clinical medicine
medicine
Fatty acid esters of hydroxy fatty
fatty acid esters of hydroxy fatty acids
Cáncer colorrectal
hydroxystearic acid
purl.org/becyt/ford/1.6 [https]
chemistry.chemical_classification
COLORECTAL CANCER
FATTY ACID ESTERS OF HYDROXY FATTY ACIDS
Mechanism (biology)
apoptosis
Fatty acid
Hydroxystearic Acid
Bioquímica y Biología Molecular
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
APOPTOSIS
HYDROXYSTEARIC ACID
030104 developmental biology
Oncology
chemistry
Biochemistry
Cell culture
Apoptosis
030220 oncology & carcinogenesis
CIENCIAS NATURALES Y EXACTAS
Function (biology)
Zdroj: UVaDOC. Repositorio Documental de la Universidad de Valladolid
instname
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Cancers
Cancers, 2019, vol. 11, no. 524, p. 1-15.
Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE)
Universidad Nacional del Nordeste
instacron:UNNE
Digital.CSIC. Repositorio Institucional del CSIC
Volume 11
Issue 4
Cancers, Vol 11, Iss 4, p 524 (2019)
ISSN: 2072-6694
DOI: 10.3390/cancers11040524
Popis: 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.
This research was funded by the Spanish Ministry of Economy, Industry and Competitiveness, grant numbers SAF2016-80883-R and SAF2015-73000-EXP. C.G. was funded by a predoctoral fellowship from the University of Valladolid (Plan de Formación de Personal Investigador). CIBERDEM is an initiative of Instituto de Salud Carlos III
We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)
Databáze: OpenAIRE
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