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Dual Behavior of Long-Chain Fatty Acids and Their Cyclooxygenase/Lipoxygenase Metabolites on Human Intestinal Caco-2 Cell Growth

  • Storniolo, Carolina E.1, 2
  • Cabral, Marisol1, 2
  • Busquets, Maria A.3, 4
  • Martín-Venegas, Raquel2, 5
  • Moreno, Juan J.1, 2, 6
  • 1 Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona , (Spain)
  • 2 Institute of Nutrition and Food Safety (INSA-UB), University of Barcelona, Barcelona , (Spain)
  • 3 Department of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona , (Spain)
  • 4 Institute of Nanosciences and Nanotechnology, University of Barcelona, Barcelona , (Spain)
  • 5 Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona , (Spain)
  • 6 CIBEROBN Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid , (Spain)
Published Article
Frontiers in Pharmacology
Frontiers Media SA
Publication Date
Sep 04, 2020
DOI: 10.3389/fphar.2020.529976
PMID: 33013380
PMCID: PMC7500452
PubMed Central


Etiology of colorectal cancer (CRC) is related, at least in part, with nutritional profile and epidemiological data indicating a key role of dietary fat on CRC pathogenesis. Moreover, inflammation and eicosanoids produced from arachidonic acid might have a pivotal role in CRC development. However, the effect of specific fatty acids (FAs) on intestinal epithelial cell growth is not completely studied now. By this reason, the aim of this work is to unravel the effect of different saturated and unsaturated long-chain fatty acids (LCFA) and some LCFA metabolites on CRC cell line growth and their possible mechanisms of action. Our results demonstrated that oleic acid is a potent mitogenic factor to Caco-2 cells, at least in part, through 10-hydroxy-8-octadecenoic synthesized by lipoxigenase pathway, whereas polyunsaturated FAs such as eicosapentaenoic (EPA) acid has a dual behavior effect depending on its concentration. A high concentration, EPA induced apoptosis through intrinsic pathway, whereas at low concentration induced cell proliferation that could be related to the synthesis of eicosanoids such as prostaglandin E3 and 12-hydroxyeicosapentaenoic acid and the subsequent induction of mitogenic cell signaling pathways (ERK 1/2, CREB, p38α). Thus, this study contributes to understand the complicated relationship between fat ingest and CRC.

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