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Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress

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Cell Stress and Chaperones Aims and scope

Abstract

Mycotoxins are considered to be significant contaminants of food and animal feed. Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. ZEN has been shown to be cytotoxic, genotoxic, and mutagenic in different cell types. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in ZEN-mediated toxicity in human intestine (HCT116) and kidney (HEK293) cells and evaluated the effects of the two common dietary compounds Quercetin (QUER) and Crocin (CRO). We show that ZEN treatment induces ER stress and activates the unfolded protein response (UPR) as evidenced by XBP1 mRNA splicing and upregulation of GRP78, ATF4, GADD34, PDIA6, and CHOP. Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis. This apoptotic process is characterized by an increase in ROS generation and lipid peroxidation, a loss of mitochondrial transmembrane potential (ΔΨm), and an activation of caspases and DNA damages. We also demonstrate that the antioxidant properties of QUER and CRO help to prevent ER stress and reduce ZEN-induced apoptosis in HCT116 and HEK293 cells. Our results suggest that antioxidant molecule might be helpful to prevent ZEN-induced ER stress and toxicity.

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Abbreviations

ZEN:

Zearalenone

CRO:

Crocin

QUER:

Quercetin

ER:

Endoplasmic reticulum

ΔΨm:

Mitochondrial transmembrane potential

mtO2 ·− :

Mitochondrial superoxide anion

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Acknowledgments

This study was supported by “Le Ministère Tunisien de l’Enseignement Supérieur, de la Recherche Scientifique et de la Technologie” and by grants from LabEx LERMIT. A. Prola received a fellowship from GRRC. A. Guilbert received a fellowship from Région Ile de France CORDDIM.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Laboratory for Research on Biologically Compatible Compounds (LRSBC), Faculty of Dental Medicine, Rue Avicenne, 5019, Monastir, Tunisia

    Intidhar Ben Salem, Manel Boussabbeh, Hassen Bacha & Salwa Abid-Essefi

  2. Faculty of Sciences of Bizerte, Carthage University, Bizerte, Tunisia

    Intidhar Ben Salem & Manel Boussabbeh

  3. INSERM UMR-S 1180, LabEx LERMIT, Châtenay-Malabry, France

    Alexandre Prola, Arnaud Guilbert & Christophe Lemaire

  4. Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France

    Christophe Lemaire

  5. Université de Versailles Saint Quentin en Yvelines, Versailles, France

    Christophe Lemaire

Authors
  1. Intidhar Ben Salem
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  2. Alexandre Prola
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  3. Manel Boussabbeh
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  4. Arnaud Guilbert
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  5. Hassen Bacha
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  6. Salwa Abid-Essefi
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  7. Christophe Lemaire
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Corresponding author

Correspondence to Salwa Abid-Essefi.

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Highlights

Zearalenone triggers ER stress in human intestinal and kidney cells

Zearalenone induces apoptosis through ER stress and activation of the mitochondrial pathway

Crocin and Quercetin protect cells against ZEN-induced ER stress and apoptosis

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Ben Salem, I., Prola, A., Boussabbeh, M. et al. Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress. Cell Stress and Chaperones 20, 927–938 (2015). https://doi.org/10.1007/s12192-015-0613-0

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