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2-Hydroxyoleic acid induces ER stress and autophagy in various human glioma cell lines

Amaia Marcilla-Etxenike1, Maria Laura Martín, Maria Antònia Noguera-Salvà

  • 1Departmento de Biología, Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Palma de Mallorca, Spain.

Plos One
|November 8, 2012
PubMed
Abstract

Insights

2-Hydroxyoleic acid (2OHOA) selectively triggers endoplasmic reticulum stress, unfolded protein response, and autophagy in human glioma cells, leading to cell cycle arrest. This compound spares normal cells, revealing its anti-cancer efficacy and lack of toxicity.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Cancer Research

Background:

  • 2-Hydroxyoleic acid (2OHOA) is a synthetic fatty acid with demonstrated anti-cancer properties and minimal side effects.
  • The precise molecular mechanisms underlying 2OHOA's selective toxicity towards human glioma cells versus normal cells remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms responsible for 2OHOA's potent anti-glioma activity.
  • To investigate the differential cellular responses of human glioma cell lines (1321N1, SF-767, U118) and normal human fibroblasts (MRC-5) to 2OHOA treatment.

Main Methods:

  • Quantitative RT-PCR and immunoblotting were employed to assess endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy markers.
  • Cellular responses were evaluated using fluorescence microscopy, electron microscopy, and flow cytometry.
  • Gene and protein expression levels of key stress and cell cycle markers were analyzed in both cancer and normal cell lines.

Main Results:

  • 2OHOA treatment significantly upregulated ER stress/UPR markers (e.g., p-eIF2α, IRE1α, CHOP, ATF4, XBP1s) in human glioma cells but not in normal MRC-5 cells.
  • Glioma cells treated with 2OHOA exhibited G(2)/M phase cell cycle arrest, accompanied by downregulation of cyclin B1 and Cdk1/Cdc2.
  • 2OHOA induced autophagy in glioma cells, evidenced by increased autophagic vesicles and upregulation of autophagy-related proteins (LC3BI/II, ATG7, ATG5), with no such effects observed in normal cells.

Conclusions:

  • 2OHOA effectively induces ER stress/UPR and autophagy selectively in human glioma cell lines.
  • These molecular events explain the compound's potent anti-cancer efficacy and its lack of toxicity towards normal cells.
  • The findings provide a mechanistic basis for the therapeutic potential of 2OHOA in glioma treatment.

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