Poorly Oxidizable Fatty Acid Analogues Inhibit the Proliferation of Cancer Cells in Culture

Berge, Kjetil; Tronstad, Karl Johan; Abdi-Dezfuli, F.; Ranheim, Trine; Mahesparan, Rupavathana; Bjerkvig, Rolf; Berge, Rolf K.

doi:10.1007/0-306-46818-2_24

Cited by 1 publication

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TTA has been shown to have both a cardioprotective effect, as well as an antiproliferative effect on cancer cells (reviewed in [10]). TTA has been found to inhibit growth of glioma [11,12], leukemia [13-16] and colon cancer cell lines [11,17] in vitro and in vivo , and hepatoma [18] and breast cancer cells [19] in vitro . TTA seems to be more potent in reducing cell growth compared with the omega-3 (n-3) PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [20].…”

Section: Introductionmentioning

confidence: 99%

“…TTA seems to be more potent in reducing cell growth compared with the omega-3 (n-3) PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [20]. A diet containing TTA has also resulted in increased vascularisation of colon cancer xenografts in mice [17] and improved the survival of mice having leukemia xenografts [11,14]. TTA food supplementation seems to be generally well tolerated by healthy persons [15,21], and TTA therefore may have a potential in cancer treatment alone or in combination with other therapies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2011

View full text Add to dashboard Cite

BackgroundPrevious 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.MethodsAn 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.ResultsTTA 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 (eIF2α) and downstream up-regulation 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/EBPβ) were enhanced, and the C/EBPβ LIP/LAP ratio was significantly increased. These results indicate prolonged ER stress and a possible link to induction of cell death.ConclusionWe find that TTA-induced growth inhibition of SW620 cells seems to be mediated through induction of ER stress and activation of the UPR pathway.

show abstract