کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5854831 1562041 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Full length articleActivation of ER stress and apoptosis by α- and β-zearalenol in HCT116 cells, protective role of Quercetin
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Full length articleActivation of ER stress and apoptosis by α- and β-zearalenol in HCT116 cells, protective role of Quercetin
چکیده انگلیسی


- α-Zearalenone and β-zearalenol trigger ER stress in human colorectal cancer cells (HCT116).
- α-Zearalenone and β-zearalenol induce apoptosis via activation of the mitochondrial pathway.
- Quercetin protect cells against α/β-zearalenol-induced ER stress and apoptosis.

Zearalenone (ZEN) and its metabolites are found in many food products and are known to induce many toxic effects. The major ZEN metabolites are α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL). The mechanisms by which they mediate their cytotoxic effects are not well known and seem to differ depending on the type of cells. We investigated the possible underlying mechanism in α-ZOL and β-ZOL-induced toxicity in HCT116 cells. We showed that cell treatment with α-ZOL/β-ZOL generated endoplasmic reticulum (ER) stress and activated the Unfolded Protein Response (UPR) as evidenced by XBP1 mRNA splicing and up-regulation of GADD34, GRP78, ATF4 and CHOP. Apoptosis was triggered by ZEN metabolites-induced ER stress, and executed through a mitochondria-dependent pathway, characterized by a loss of mitochondrial transmembrane potential (ΔΨm), a downstream generation of O2
- − and caspase 3 activation. Cellular deficiency of the pro-apoptotic proteins Bax and Bak protected cells against α/β-ZOL-induced toxicity. However, treatment with α-ZOL or β-ZOL combined with Quercetin (QUER), a common dietary flavonoid with well-known antioxidant activity, significantly reduced damage induced by α and β-ZOL in all tested markers. We concluded that QUER protects against the cellular toxicity of α and β-ZOL.×

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 53, March 2016, Pages 334-342
نویسندگان
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