Methyleugenol and selected oxidative metabolites affect DNA-Damage signalling pathways and induce apoptosis in human colon tumour HT29 cells
Copyright © 2017. Published by Elsevier Ltd..
Previously the food carcinogen methyleugenol was found to be cytotoxic and genotoxic in multiple cell lines and in primary hepatocytes. In this study, the question addressed was whether methyleugenol and the selected oxidative metabolites, 1'-hydroxymethyleugenol, methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol trigger a DNA damage response in the human colon carcinoma HT29 cell line. Most notably investigations by flow cytometry revealed that the metabolites induce an accumulation of HT29 cells in the G2 phase of the cell cycle. DNA damage response is characterised by a time-delayed phosphorylation of ATM (ataxia-telangiectasia, mutated)/ATR (ATM- and Rad3-related) kinases and checkpoint kinase 1 after 2 h of incubation, and the tumour suppressor protein p53 only after 24 h of incubation. The test compounds induced apoptotic cell death indicated by cleavage of caspase 3 and poly-(ADP-ribose)-polymerase after a prolonged incubation time up to 72 h. In addition, activation of ATM/ATR-signalling cascade might contribute to apoptosis induction to a certain extent. However, clarification of this relationship awaits experimental confirmation.
| Errataetall: |
ErratumIn: Food Chem Toxicol. 2018 Apr 4;115:413. - PMID 29626800 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:108 |
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| Enthalten in: |
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association - 108(2017), Pt A vom: 01. Okt., Seite 267-275 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Groh, Isabel Anna Maria [VerfasserIn] |
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| Links: |
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| Themen: |
29T9VA6R7M |
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| Anmerkungen: |
Date Completed 05.01.2018 Date Revised 07.04.2018 published: Print-Electronic ErratumIn: Food Chem Toxicol. 2018 Apr 4;115:413. - PMID 29626800 Citation Status MEDLINE |
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| doi: |
10.1016/j.fct.2017.08.014 |
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| Förderinstitution / Projekttitel: |
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| 500 | |a ErratumIn: Food Chem Toxicol. 2018 Apr 4;115:413. - PMID 29626800 | ||
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| 520 | |a Copyright © 2017. Published by Elsevier Ltd. | ||
| 520 | |a Previously the food carcinogen methyleugenol was found to be cytotoxic and genotoxic in multiple cell lines and in primary hepatocytes. In this study, the question addressed was whether methyleugenol and the selected oxidative metabolites, 1'-hydroxymethyleugenol, methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol trigger a DNA damage response in the human colon carcinoma HT29 cell line. Most notably investigations by flow cytometry revealed that the metabolites induce an accumulation of HT29 cells in the G2 phase of the cell cycle. DNA damage response is characterised by a time-delayed phosphorylation of ATM (ataxia-telangiectasia, mutated)/ATR (ATM- and Rad3-related) kinases and checkpoint kinase 1 after 2 h of incubation, and the tumour suppressor protein p53 only after 24 h of incubation. The test compounds induced apoptotic cell death indicated by cleavage of caspase 3 and poly-(ADP-ribose)-polymerase after a prolonged incubation time up to 72 h. In addition, activation of ATM/ATR-signalling cascade might contribute to apoptosis induction to a certain extent. However, clarification of this relationship awaits experimental confirmation | ||
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