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

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 ZENmediated 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.

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

“…Transcriptional activation of CHOP plays an important role in ER stress-induced apoptosis in cells [34]. Furthermore, a prior study reported similar data in human colon HCT116 cells and human kidney HEK293 cells [35]. In this cell culture study, ZEN induced ER stress and ER stress-mediated cell death through the CHOP pathway.…”

Bacillus velezensis A2 fermentation exerts a protective effect on renal injury induced by Zearalenone in mice

“…Previous studies have shown that the ER stress pathway has been reported to participate in oxidative damage and apoptosis induced by ZEN 22 – 24 , 46 . To provide further evidence that the A2 fermentation broth exerts a protective effect from ZEN-induced kidney injury, we explored whether the A2 fermentation broth could decrease both ER stress and apoptosis induced by ZEN.…”

“…Additionally, ZEN could alter the enzymatic and hematological parameters of mice, and it could induce higher levels of oxidative stress 19 – 21 . Meanwhile, ZEN-induced apoptosis is characterized by ROS production and increased lipid peroxidation 22 , 23 . A previous study demonstrated that ZEN induced apoptosis in RAW 264.7 macrophages through endoplasmic reticulum stress (ER stress) 24 .…”

The Significance of Regulatory MicroRNAs: Their Roles in Toxicodynamics of Mycotoxins and in the Protection Offered by Dietary Therapeutics Against Mycotoxin‐Induced Toxicity

“…Lipoic acid and vitamin C were evaluated in vivo in terms of their abilities to alleviate the liver oxidative damage induced by AFB1 or ZEA, and vitamin C was found to alleviate the damage via regulating the nuclear receptor signaling pathway with changes of nuclear receptor genes (PXR, constitutive active receptor [CAR]) (Ma et al., ; Shi et al., ). Crocin with a high antioxidant capacity was found to protect HEK293 cells and human colon carcinoma (HCT116) cells against apoptosis and endoplasmic reticulum stress induced by ZEA and its 2 metabolites (Ben Salem et al., , ). Carotenoids such as lycopene were found to exhibit protection against ZEA‐induced oxidative stress, inflammatory and reproductive damages, and OTA‐induced DNA damage in male mice (Aydin et al., ; Boeira et al., ).…”