Reference - Detail
|Author||Iwao C, Shidoji Y.|
|Title||Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.|
The acyclic diterpenoid acid geranylgeranoic acid (GGA) has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1) GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2) all-trans retinoic acid induces XBP1 splicing but little cell death; and 3) phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR) and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.
|MeSH||Carcinoma, Hepatocellular / pathology* Cell Death / drug effects Cell Line, Tumor Cell Nucleus / drug effects Cell Nucleus / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Diterpenes / chemistry Diterpenes / pharmacology* Fatty Acids, Unsaturated / chemistry Fatty Acids, Unsaturated / pharmacology* Humans Inhibitory Concentration 50 Liver Neoplasms / pathology* Microtubule-Associated Proteins / metabolism Oleic Acid / pharmacology Palmitates / pharmacology RNA Splicing / drug effects RNA Splicing / genetics Regulatory Factor X Transcription Factors Transcription Factors / genetics Transcription Factors / metabolism Unfolded Protein Response / drug effects* X-Box Binding Protein 1|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|
|Human and Animal Cells|