3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells

Understanding the effects induced by carcinogens on primary colonic epithelial cells and how to counteract them might help to prevent colon cancer, which is one of the most frequent and aggressive cancers. In this study, we exposed primary human colonic epithelial cells (HCoEpC) to Benzo[a]pyrene (B...

Full description

Bibliographic Details
Main Authors: Roberta Santarelli, Chiara Pompili, Maria Saveria Gilardini Montani, Lorenzo Evangelista, Roberta Gonnella, Mara Cirone
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/3/663
_version_ 1797443568345808896
author Roberta Santarelli
Chiara Pompili
Maria Saveria Gilardini Montani
Lorenzo Evangelista
Roberta Gonnella
Mara Cirone
author_facet Roberta Santarelli
Chiara Pompili
Maria Saveria Gilardini Montani
Lorenzo Evangelista
Roberta Gonnella
Mara Cirone
author_sort Roberta Santarelli
collection DOAJ
description Understanding the effects induced by carcinogens on primary colonic epithelial cells and how to counteract them might help to prevent colon cancer, which is one of the most frequent and aggressive cancers. In this study, we exposed primary human colonic epithelial cells (HCoEpC) to Benzo[a]pyrene (B[a]P) and found that it led to an increased production of pro-inflammatory cytokines and activated ERK1/2 and mTOR. These pathways are known to be involved in inflammatory bowel disease (IBD), which represents a colon cancer risk factor. Moreover, B[a]P reduced autophagy and mitophagy, processes whose dysregulation has been clearly demonstrated to predispose to cancer either by in vitro or in vivo studies. Interestingly, all the effects induced by B[a]P could be counteracted by 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol, H), the most powerful anti-inflammatory and antioxidant compound contained in olive oil. This study sheds light on the mechanisms that could be involved in colon carcinogenesis induced by a chemical carcinogen and identifies a safe natural product that may help to prevent them.
first_indexed 2024-03-09T12:57:58Z
format Article
id doaj.art-83b283fb53ae4764a290979bd04386d0
institution Directory Open Access Journal
issn 1999-4923
language English
last_indexed 2024-03-09T12:57:58Z
publishDate 2022-03-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj.art-83b283fb53ae4764a290979bd04386d02023-11-30T21:58:08ZengMDPI AGPharmaceutics1999-49232022-03-0114366310.3390/pharmaceutics140306633,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial CellsRoberta Santarelli0Chiara Pompili1Maria Saveria Gilardini Montani2Lorenzo Evangelista3Roberta Gonnella4Mara Cirone5Department of Experimental Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, 00185 Rome, ItalyUnderstanding the effects induced by carcinogens on primary colonic epithelial cells and how to counteract them might help to prevent colon cancer, which is one of the most frequent and aggressive cancers. In this study, we exposed primary human colonic epithelial cells (HCoEpC) to Benzo[a]pyrene (B[a]P) and found that it led to an increased production of pro-inflammatory cytokines and activated ERK1/2 and mTOR. These pathways are known to be involved in inflammatory bowel disease (IBD), which represents a colon cancer risk factor. Moreover, B[a]P reduced autophagy and mitophagy, processes whose dysregulation has been clearly demonstrated to predispose to cancer either by in vitro or in vivo studies. Interestingly, all the effects induced by B[a]P could be counteracted by 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol, H), the most powerful anti-inflammatory and antioxidant compound contained in olive oil. This study sheds light on the mechanisms that could be involved in colon carcinogenesis induced by a chemical carcinogen and identifies a safe natural product that may help to prevent them.https://www.mdpi.com/1999-4923/14/3/663Benzo[a]pyrene3,4-DihydroxyphenylethanolHydroxytyrosolhuman colonic epithelial cellsautophagyERK
spellingShingle Roberta Santarelli
Chiara Pompili
Maria Saveria Gilardini Montani
Lorenzo Evangelista
Roberta Gonnella
Mara Cirone
3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells
Pharmaceutics
Benzo[a]pyrene
3,4-Dihydroxyphenylethanol
Hydroxytyrosol
human colonic epithelial cells
autophagy
ERK
title 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells
title_full 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells
title_fullStr 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells
title_full_unstemmed 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells
title_short 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells
title_sort 3 4 dihydroxyphenylethanol dpe or hydroxytyrosol counteracts erk1 2 and mtor activation pro inflammatory cytokine release autophagy and mitophagy reduction mediated by benzo a pyrene in primary human colonic epithelial cells
topic Benzo[a]pyrene
3,4-Dihydroxyphenylethanol
Hydroxytyrosol
human colonic epithelial cells
autophagy
ERK
url https://www.mdpi.com/1999-4923/14/3/663
work_keys_str_mv AT robertasantarelli 34dihydroxyphenylethanoldpeorhydroxytyrosolcounteractserk12andmtoractivationproinflammatorycytokinereleaseautophagyandmitophagyreductionmediatedbybenzoapyreneinprimaryhumancolonicepithelialcells
AT chiarapompili 34dihydroxyphenylethanoldpeorhydroxytyrosolcounteractserk12andmtoractivationproinflammatorycytokinereleaseautophagyandmitophagyreductionmediatedbybenzoapyreneinprimaryhumancolonicepithelialcells
AT mariasaveriagilardinimontani 34dihydroxyphenylethanoldpeorhydroxytyrosolcounteractserk12andmtoractivationproinflammatorycytokinereleaseautophagyandmitophagyreductionmediatedbybenzoapyreneinprimaryhumancolonicepithelialcells
AT lorenzoevangelista 34dihydroxyphenylethanoldpeorhydroxytyrosolcounteractserk12andmtoractivationproinflammatorycytokinereleaseautophagyandmitophagyreductionmediatedbybenzoapyreneinprimaryhumancolonicepithelialcells
AT robertagonnella 34dihydroxyphenylethanoldpeorhydroxytyrosolcounteractserk12andmtoractivationproinflammatorycytokinereleaseautophagyandmitophagyreductionmediatedbybenzoapyreneinprimaryhumancolonicepithelialcells
AT maracirone 34dihydroxyphenylethanoldpeorhydroxytyrosolcounteractserk12andmtoractivationproinflammatorycytokinereleaseautophagyandmitophagyreductionmediatedbybenzoapyreneinprimaryhumancolonicepithelialcells