Hydroxytyrosol attenuates tunicamycin‐induced endoplasmic reticulum stress in human hepatocarcinoma cells

• Published in: Molecular nutrition & food research 2014-05, Vol.58 (5), p.954-962
• Main Authors: Giordano, Elena, Davalos, Alberto, Nicod, Nathalie, Visioli, Francesco
• Format: Article
• Language: English
• Subjects: Antioxidants; Antioxidants - pharmacology; Biological and medical sciences; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; enzyme-linked immunosorbent assay; ER stress; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glutathione - analogs & derivatives; Glutathione - pharmacology; Hep G2 Cells; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Hydroxytyrosol; Lipid Metabolism - drug effects; lipid peroxidation; lipoic acid; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; low density lipoprotein; Mediterranean diet; Olea - chemistry; Olive Oil; olives; oxidation; phenolic compounds; Phenols - pharmacology; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; Plant Extracts - pharmacology; Plant Oils - chemistry; Polyphenols; reverse transcriptase polymerase chain reaction; Risk Factors; Signal Transduction; Thioctic Acid - pharmacology; tunicamycin; Tunicamycin - adverse effects; Unfolded Protein Response; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Western blotting
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201300465

SCOPE: Hydroxytyrosol (HT) is a phenolic compound peculiarly abundant in olives and it is being recognized as a protector of LDL from oxidation. In addition to lipid oxidation, one emerging risk factor for cardiovascular disease is ER stress. We tested the effect of HT on the modulation of ER stress in HepG2 cells. METHODS AND RESULTS: HepG2 cells were treated with 1 μM and 5 μM of HT and 100 μM lipoic acid (LA) and glutathione—ethyl ester (GSH), for 24 h. Induction of the unfolded protein response (UPR) was initiated by treatment with 2 μg/mL tunicamycin for 4 h. Real time RT‐PCR analyses followed by Western blot and ELISA of different ER stress markers revealed that the protective activities of HT were superior to those of two known thiolic antioxidants, i.e., LA and GSH. CONCLUSION: Mounting evidence indicates the ER as an important target of dietary or pharmacological intervention. In this paper, we report the modulatory activities of physiological concentrations of HT toward ER stress and we shed some light on pathways alternative to the well‐known antioxidant mechanisms, through which olive oil phenolics modulate cell signaling and could impact cardiovascular health and degenerative diseases.