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

被引:50
|
作者
Rodriguez, Juan P. [1 ,2 ]
Guijas, Carlos [1 ,3 ]
Astudillo, Alma M. [1 ,3 ]
Rubio, Julio M. [1 ,3 ]
Balboa, Maria A. [1 ,3 ]
Balsinde, Jesus [1 ,3 ]
机构
[1] Univ Valladolid, Inst Biol & Genet Mol, CSIC, Valladolid 47003, Spain
[2] Univ Nacl Nordeste, Lab Invest Bioquim, Inst Quim Bas & Aplicada Nordeste Argentino IQUIB, Consejo Nacl Invest Cient & Tecn UNNE CONICET,Fac, RA-3400 Corrientes, Argentina
[3] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid 28029, Spain
来源
CANCERS | 2019年 / 11卷 / 04期
关键词
colorectal cancer; hydroxystearic acid; fatty acid esters of hydroxy fatty acids; apoptosis; CYTOSOLIC GROUP IVA; ARACHIDONIC-ACID; PHOSPHOLIPASE A(2); MACROPHAGES; EICOSANOIDS; INHIBITION; MONOCYTES; HYDRATION; SYSTEM; LIPIDS;
D O I
10.3390/cancers11040524
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页数:15
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