The mycotoxin zearalenone enhances cell proliferation, colony formation and promotes cell migration in the human colon carcinoma cell line HCT116

Abassi, Haila; Ayed-Boussema, Imen; Shirley, Sarah; Abid, Salwa; Bacha, Hassen; Micheau, Olivier

doi:10.1016/j.toxlet.2016.04.012

Cited by 49 publications

(29 citation statements)

References 37 publications

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“…Furthermore, several studies have showed that since ZEA can cause DNA damage and lesions, which can induce mutations, ZEA also exerts carcinogenic properties. The results presented in the current study provided the evidence that causing oxidative stress and ER stress were important methods for ZEA to exert their cytotoxicity [ 31 , 32 ]. Further explorations are needed to detect how ZEA influences cell growth and death.…”

Section: Discussionmentioning

confidence: 86%

ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

Zheng

Wang

et al. 2018

Toxins

102

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Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins, cell death, cell apoptosis, ROS generation and the ATP/AMPK pathway in Sertoli cells. The role of ROS, ER stress and the ATP/AMPK pathway in ZEA-induced cell-cycle arrest and cell apoptosis was explored by using the antioxidant NAC, ER stress inhibitor 4-PBA and the AMPK inhibitor dorsomorphin, respectively. The results revealed that ZEA inhibited the cell proliferation, influenced the distribution of the cell cycle and induced cell apoptosis through the ATP/AMPK pathway. The ATP/AMPK pathway was regulated by ER stress that was induced by ROS generation after exposure to ZEA. Taking these together, this study provided evidence that ROS regulated the process of ZEA-induced cell cycle arrest and cell apoptosis through ER stress and the ATP/AMPK signal ways.Keywords: Zearalenone; cell cycle; cell apoptosis; ROS; ER stress; AMPK signaling; Sertoli cells Key Contribution: Zearalenone induced the cell cycle arrest and apoptosis through ROS-ER stress-AMPK pathway in mouse sertoli cells.

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Section: Discussionmentioning

confidence: 86%

ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

Zheng

Wang

et al. 2018

Toxins

102

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“…This fact sustained by other environmental toxic agents can be an essential in the activation of tumor initiation [ 34 ]. In the case of HCT116 cells it was observed that even at low concentration ZEA increase cell proliferation, colony formation and cell migration [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Microarray based gene expression analysis of Sus Scrofa duodenum exposed to zearalenone: significance to human health

et al. 2016

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BackgroundZearalenone (ZEA) is a secondary metabolite produced by Fusarium species. ZEA was proved to exert a wide range of unwanted side effects, but its mechanism of action, particularly at duodenum levels, remains unclear. In our study based on the microarray technology we assessed the alteration of gene expression pattern Sus scrofa duodenum which has been previously exposed to ZEA. Gene expression data was validated by qRT-PCR and ELISA. The gene expression data were further extrapolated the results to their human orthologues and analyzed the data in the context of human health using IPA (Ingenuity Pathways Analysis).ResultsUsing Agilent microarray technology, we found that gene expression pattern was significantly affected by ZEA exposure, considering a 2-fold expression difference as a cut-off level and a p-value < 0.05. In total, we found 1576 upregulated and 2446 downregulated transcripts. About 1084 genes (764 downregulated and 751 overexpressed) were extrapolated to their human orthologues. IPA analysis showed various altered key cellular and molecular pathways. As expected, we observed a significant alteration of immune response related genes, MAPK (mitogen activate protein kinases) pathways or Toll-Like Receptors (TLRs). What captured our attention was the modulation of pathways related to the activation of early carcinogenesis.ConclusionsOur data demonstrate that ZEA has a complex effect at duodenum level. ZEA is able to activate not only the immune response related genes, but also those relate to colorectal carcinogenesis. The effects can be more dramatic when connected with the exposure to other environmental toxic agents or co-occurrence with different microorganisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2984-8) contains supplementary material, which is available to authorized users.

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“…The study showed that ZEA and its metabolites acted differently in the gut (Marin et al, 2015 ). Abassi et al ( 2016 ) demonstrated that ZEA enhanced cell proliferation, increased colony formation and fastened cell migration of colon carcinoma cell line HCT116. Another study also showed that ZEA down-regulated the expression of tumor-suppressor genes (PCDH11X, DKK1, and TC5313860) in intestinal cells (Taranu et al, 2015 ).…”

Section: Gastrointestinal Tractmentioning

confidence: 99%

Mycotoxin: Its Impact on Gut Health and Microbiota

Liew

Sabran

2018

Front. Cell. Infect. Microbiol.

336

195

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The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and mycotoxicosis.

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The mycotoxin zearalenone enhances cell proliferation, colony formation and promotes cell migration in the human colon carcinoma cell line HCT116

Cited by 49 publications

References 37 publications

ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

Microarray based gene expression analysis of Sus Scrofa duodenum exposed to zearalenone: significance to human health

Mycotoxin: Its Impact on Gut Health and Microbiota

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