, Volume 44, Issue 8, pp 673–683

Docosahexaenoic Acid Activates Some SREBP-2 Targets Independent of Cholesterol and ER Stress in SW620 Colon Cancer Cells

  • Gro Leite Størvold
  • Karianne Giller Fleten
  • Cathrine Goberg Olsen
  • Turid Follestad
  • Hans Einar Krokan
  • Svanhild Arentz Schønberg
Original Article


The SREBP-2 transcription factor is mainly activated by low cellular cholesterol levels. However, other factors may also cause SREBP-2 activation. We have previously demonstrated activation of SREBP-2 by the polyunsaturated fatty acid docosahexaenoic acid (DHA) in SW620 colon cancer cells. Despite activation of SREBP-2, only a few target genes were induced and cholesterol biosynthesis was reduced. In the present study, gene expression analysis at early time points verified the previously observed SREBP-2 target gene expression pattern. Activation of SREBP-2 using siRNAs targeting Niemann Pick C1 protein (NPC1) led to increased expression of all SREBP target genes examined, indicating that activation of some SREBP-2 target genes is inhibited during DHA-treatment. Cholesterol supplementation during DHA treatment did not abolish SREBP-2 activation. We also demonstrate that activation of SREBP-2 is independent of ER stress and eIF2α phosphorylation, which we have previously observed in DHA-treated cells. Thapsigargin-induced ER stress repressed expression of SREBP-2 target genes, but with a different pattern than observed in DHA-treated cells. Moreover, oleic acid (OA) treatment, which does not induce ER stress in SW620 cells, led to activation of SREBP-2 and induced a target gene expression pattern similar to that of DHA-treated cells. These results indicate that DHA and OA may activate SREBP-2 and inhibit activation of SREBP-2 target genes through a mechanism independent of cholesterol level and ER stress.


SREBP-2 Cholesterol biosynthesis ER stress Transcriptional regulation eIF2α 



Activating transcription factor 6


Docosahexaenoic acid


DnaJ (Hsp 40) homolog-subfamily A-member 4


Endoplasmic reticulum


Eukaryote translation initiation factor 2 alpha


Fatty acid


Farnesyl diphosphate farnesyltransferase


3-Hydroxy-3-methylglutaryl-coenzyme A reductase


Isopentenyl-diphosphate delta isomerase


Insulin induced gene


Low density lipoprotein receptor


Niemann Pick C1


Oleic acid


Polyunsaturated fatty acid


SREBP cleavage activating protein


Small interfering RNA


Sterol regulatory element


SRE binding protein


Mature SREBP


Squalene synthetase




Unsaturated fatty acid


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Copyright information

© AOCS 2009

Authors and Affiliations

  • Gro Leite Størvold
    • 1
  • Karianne Giller Fleten
    • 1
  • Cathrine Goberg Olsen
    • 1
  • Turid Follestad
    • 2
  • Hans Einar Krokan
    • 3
  • Svanhild Arentz Schønberg
    • 1
  1. 1.Department of Laboratory Medicine, Children’s and Women’s HealthNorwegian University of Science and Technology (NTNU)TrondheimNorway
  2. 2.Department of Mathematical SciencesNorwegian University of Science and Technology (NTNU)TrondheimNorway
  3. 3.Department of Cancer Research and Molecular MedicineNorwegian University of Science and Technology (NTNU)TrondheimNorway

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