Cargando…

Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway

Colorectal cancer (CRC) is one of the most well-known malignancies with high prevalence and poor 5-year survival. Previous studies have demonstrated that a high-fat diet (HFD) is capable of increasing the odds of developing CRC. Acrolein, an IARC group 2A carcinogen, can be formed from carbohydrates...

Descripción completa

Detalles Bibliográficos
Autores principales: Tsai, Hong-Chieh, Tsou, Han-Hsing, Lin, Chun-Chi, Chen, Shao-Chen, Cheng, Hsiao-Wei, Liu, Tsung-Yun, Chen, Wei-Shone, Jiang, Jeng-Kai, Yang, Shung-Haur, Chang, Shih-Ching, Teng, Hao-Wei, Wang, Hsiang-Tsui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206110/
https://www.ncbi.nlm.nih.gov/pubmed/34131238
http://dx.doi.org/10.1038/s41598-021-92035-z
_version_ 1783708577972617216
author Tsai, Hong-Chieh
Tsou, Han-Hsing
Lin, Chun-Chi
Chen, Shao-Chen
Cheng, Hsiao-Wei
Liu, Tsung-Yun
Chen, Wei-Shone
Jiang, Jeng-Kai
Yang, Shung-Haur
Chang, Shih-Ching
Teng, Hao-Wei
Wang, Hsiang-Tsui
author_facet Tsai, Hong-Chieh
Tsou, Han-Hsing
Lin, Chun-Chi
Chen, Shao-Chen
Cheng, Hsiao-Wei
Liu, Tsung-Yun
Chen, Wei-Shone
Jiang, Jeng-Kai
Yang, Shung-Haur
Chang, Shih-Ching
Teng, Hao-Wei
Wang, Hsiang-Tsui
author_sort Tsai, Hong-Chieh
collection PubMed
description Colorectal cancer (CRC) is one of the most well-known malignancies with high prevalence and poor 5-year survival. Previous studies have demonstrated that a high-fat diet (HFD) is capable of increasing the odds of developing CRC. Acrolein, an IARC group 2A carcinogen, can be formed from carbohydrates, vegetable oils, animal fats, and amino acids through the Maillard reaction during the preparation of foods. Consequently, humans are at risk of acrolein exposure through the consumption of foods rich in fat. However, whether acrolein contributes to HFD-induced CRC has not been determined. In this study, we found that acrolein induced oncogenic transformation, including faster cell cycling, proliferation, soft agar formation, sphere formation and cell migration, in NIH/3T3 cells. Using xenograft tumorigenicity assays, the acrolein-transformed NIH/3T3 clone formed tumors. In addition, cDNA microarray and bioinformatics studies by Ingenuity Pathway Analysis pointed to the fact that RAS/MAPK pathway was activated in acrolein-transformed clones that contributed to colon tumorigenesis. Furthermore, acrolein-induced DNA damages (Acr-dG adducts) were higher in CRC tumor tissues than in normal epithelial cells in CRC patients. Notably, CRC patients with higher levels of Acr-dG adducts appeared to have better prognosis. The results of this study demonstrate for the first time that acrolein is important in oncogenic transformation through activation of the RAS/MAPK signaling pathway, contributing to colon tumorigenesis.
format Online
Article
Text
id pubmed-8206110
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-82061102021-06-16 Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway Tsai, Hong-Chieh Tsou, Han-Hsing Lin, Chun-Chi Chen, Shao-Chen Cheng, Hsiao-Wei Liu, Tsung-Yun Chen, Wei-Shone Jiang, Jeng-Kai Yang, Shung-Haur Chang, Shih-Ching Teng, Hao-Wei Wang, Hsiang-Tsui Sci Rep Article Colorectal cancer (CRC) is one of the most well-known malignancies with high prevalence and poor 5-year survival. Previous studies have demonstrated that a high-fat diet (HFD) is capable of increasing the odds of developing CRC. Acrolein, an IARC group 2A carcinogen, can be formed from carbohydrates, vegetable oils, animal fats, and amino acids through the Maillard reaction during the preparation of foods. Consequently, humans are at risk of acrolein exposure through the consumption of foods rich in fat. However, whether acrolein contributes to HFD-induced CRC has not been determined. In this study, we found that acrolein induced oncogenic transformation, including faster cell cycling, proliferation, soft agar formation, sphere formation and cell migration, in NIH/3T3 cells. Using xenograft tumorigenicity assays, the acrolein-transformed NIH/3T3 clone formed tumors. In addition, cDNA microarray and bioinformatics studies by Ingenuity Pathway Analysis pointed to the fact that RAS/MAPK pathway was activated in acrolein-transformed clones that contributed to colon tumorigenesis. Furthermore, acrolein-induced DNA damages (Acr-dG adducts) were higher in CRC tumor tissues than in normal epithelial cells in CRC patients. Notably, CRC patients with higher levels of Acr-dG adducts appeared to have better prognosis. The results of this study demonstrate for the first time that acrolein is important in oncogenic transformation through activation of the RAS/MAPK signaling pathway, contributing to colon tumorigenesis. Nature Publishing Group UK 2021-06-15 /pmc/articles/PMC8206110/ /pubmed/34131238 http://dx.doi.org/10.1038/s41598-021-92035-z Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tsai, Hong-Chieh
Tsou, Han-Hsing
Lin, Chun-Chi
Chen, Shao-Chen
Cheng, Hsiao-Wei
Liu, Tsung-Yun
Chen, Wei-Shone
Jiang, Jeng-Kai
Yang, Shung-Haur
Chang, Shih-Ching
Teng, Hao-Wei
Wang, Hsiang-Tsui
Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway
title Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway
title_full Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway
title_fullStr Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway
title_full_unstemmed Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway
title_short Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway
title_sort acrolein contributes to human colorectal tumorigenesis through the activation of ras-mapk pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206110/
https://www.ncbi.nlm.nih.gov/pubmed/34131238
http://dx.doi.org/10.1038/s41598-021-92035-z
work_keys_str_mv AT tsaihongchieh acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT tsouhanhsing acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT linchunchi acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT chenshaochen acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT chenghsiaowei acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT liutsungyun acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT chenweishone acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT jiangjengkai acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT yangshunghaur acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT changshihching acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT tenghaowei acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
AT wanghsiangtsui acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway