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Tetradecylthioacetic acid inhibits proliferation of human SW620 colon cancer cells - gene expression profiling implies endoplasmic reticulum stress

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dc.contributor.author Lundemo, Anne G.
dc.contributor.author Pettersen, Caroline H.H.
dc.contributor.author Berge, Kjetil
dc.contributor.author Berge, Rolf K.
dc.contributor.author Schønberg, Svanhild A.
dc.date.accessioned 2012-01-18T13:01:13Z
dc.date.available 2012-01-18T13:01:13Z
dc.date.issued 2011-10-25
dc.identifier.citation Lipids in Health and Disease 2011, 10:190 en
dc.identifier.issn 1476-511X
dc.identifier.uri http://dx.doi.org/10.1186/1476-511X-10-190
dc.identifier.uri http://hdl.handle.net/1956/5466
dc.description.abstract Background: Previous reports have shown an antiproliferative effect of the synthetic, 3-thia fatty acid tetradecylthioacetic acid (TTA) on different cancer cells in vitro and in vivo. The mechanisms behind the observed effects are poorly understood. We therefore wanted to explore the molecular mechanisms involved in TTA-induced growth inhibition of the human colon cancer cell line SW620 by gene expression profiling. Methods: An antiproliferative effect of TTA on SW620 cells in vitro was displayed in real time using the xCELLigence System (Roche). Affymetrix gene expression profiling was performed to elucidate the molecular mechanisms behind the antiproliferative effect of TTA. Changes in gene expression were verified at protein level by western blotting. Results: TTA reduced SW620 cell growth, measured as baseline cell index, by 35% and 55% after 48 h and 72 h, respectively. We show for the first time that TTA induces an endoplasmic reticulum (ER) stress response in cancer cells. Gene expression analysis revealed changes related to ER stress and unfolded protein response (UPR). This was verified at protein level by phosphorylation of eukaryote translation initiation factor 2 alpha (eIF2a) and downstream upregulation of activating transcription factor 4 (ATF4). Transcripts for positive and negative cell cycle regulators were down- and up-regulated, respectively. This, together with a down-regulation of Cyclin D1 at protein level, indicates inhibition of cell cycle progression. TTA also affected transcripts involved in calcium homeostasis. Moreover, mRNA and protein level of the ER stress inducible C/EBP-homologous protein (CHOP), Tribbles homolog 3 (Drosophila) (TRIB3) and CCAAT/enhancer binding protein beta (C/EBPb) were enhanced, and the C/EBPb LIP/LAP ratio was significantly increased. These results indicate prolonged ER stress and a possible link to induction of cell death. Conclusion: We find that TTA-induced growth inhibition of SW620 cells seems to be mediated through induction of ER stress and activation of the UPR pathway. en
dc.language.iso eng en
dc.publisher BioMed Central en
dc.rights Copyright 2011 Lundemo et al; licensee BioMed Central Ltd. en
dc.rights.uri http://creativecommons.org/licenses/by/2.0/ en
dc.subject Endoplasmic reticulum stress en
dc.title Tetradecylthioacetic acid inhibits proliferation of human SW620 colon cancer cells - gene expression profiling implies endoplasmic reticulum stress en
dc.type Peer reviewed en
dc.type Journal article en
dc.subject.nsi VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 en
dc.type.version publishedVersion en


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Copyright 2011 Lundemo et al; licensee BioMed Central Ltd. Except where otherwise noted, this item's license is described as Copyright 2011 Lundemo et al; licensee BioMed Central Ltd.

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