Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis

  • Authors: Natalia Scaglia, R. Ariel Igal
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  • Published online on: Wednesday, October 1, 2008
  • Pages: 839-850
  • DOI: 10.3892/ijo_00000072

Abstract

Saturated (SFA) and monounsaturated (MUFA) fatty acids, the most abundant fatty acid species, have many divergent biological effects including the regulation of cell proliferation, programmed cell death and lipid-mediated cytotoxicity. Their distribution is regulated by Stearoyl-CoA Desaturases (SCD), the enzymes that convert SFA into MUFA. A positive correlation between high levels of tissue MUFA and several types of cancer has been reported, but a causal relationship between the function of SCD1, the main human SCD isoform, and cancer development has not yet been firmly established. Here we report that the stable knockdown of SCD1 gene expression in A549 human lung adenocarcinoma cells decreased the ratio MUFA/SFA in total lipids and inhibited the incorporation of glucose into cell lipids. Cell proliferation and anchorage-independent growth were considerably decreased in SCD1-depleted cells, whereas the rate of apoptosis was elevated, with respect to control A549 cells. In addition, phosphorylation of Akt-Ser473 and GSK-3β-Ser9 was found notably impaired in SCD1-ablated A549 cells. Interestingly, the effects of SCD1 blockade on Akt activation, cancer cell growth and apoptosis could not be reversed by exogenously added oleic acid. Remarkably, the reduction of SCD1 expression in lung cancer cells significantly delayed the formation of tumors and reduced the growth rate of tumor xenografts in mice. Our study demonstrates that SCD1 activity regulates Akt activation and determines the rate of cell proliferation, survival and invasiveness in A549 cancer cells and shows, for the first time, that SCD1 is a key factor in the regulation of tumorigenesis in vivo.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Scaglia, N., & Igal, R. (2008). Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis. International Journal of Oncology, 33(4), 839-850.
MLA
Scaglia, and R. Igal. "Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis." International Journal of Oncology International Journal of Oncology 33.4 (2008): 839-850.
Chicago
Scaglia, and R. Igal. "Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 839-850.