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

Abstract 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 carb...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hong-Chieh Tsai, Han-Hsing Tsou, Chun-Chi Lin, Shao-Chen Chen, Hsiao-Wei Cheng, Tsung-Yun Liu, Wei-Shone Chen, Jeng-Kai Jiang, Shung-Haur Yang, Shih-Ching Chang, Hao-Wei Teng, Hsiang-Tsai Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5177caa898a641d98b6a15973fb91965
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5177caa898a641d98b6a15973fb91965
record_format	dspace
spelling	oai:doaj.org-article:5177caa898a641d98b6a15973fb919652021-12-02T17:40:48ZAcrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway10.1038/s41598-021-92035-z2045-2322https://doaj.org/article/5177caa898a641d98b6a15973fb919652021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92035-zhttps://doaj.org/toc/2045-2322Abstract 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.Hong-Chieh TsaiHan-Hsing TsouChun-Chi LinShao-Chen ChenHsiao-Wei ChengTsung-Yun LiuWei-Shone ChenJeng-Kai JiangShung-Haur YangShih-Ching ChangHao-Wei TengHsiang-Tsai WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hong-Chieh Tsai Han-Hsing Tsou Chun-Chi Lin Shao-Chen Chen Hsiao-Wei Cheng Tsung-Yun Liu Wei-Shone Chen Jeng-Kai Jiang Shung-Haur Yang Shih-Ching Chang Hao-Wei Teng Hsiang-Tsai Wang Acrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathway
description	Abstract 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	article
author	Hong-Chieh Tsai Han-Hsing Tsou Chun-Chi Lin Shao-Chen Chen Hsiao-Wei Cheng Tsung-Yun Liu Wei-Shone Chen Jeng-Kai Jiang Shung-Haur Yang Shih-Ching Chang Hao-Wei Teng Hsiang-Tsai Wang
author_facet	Hong-Chieh Tsai Han-Hsing Tsou Chun-Chi Lin Shao-Chen Chen Hsiao-Wei Cheng Tsung-Yun Liu Wei-Shone Chen Jeng-Kai Jiang Shung-Haur Yang Shih-Ching Chang Hao-Wei Teng Hsiang-Tsai Wang
author_sort	Hong-Chieh Tsai
title	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_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_sort	acrolein contributes to human colorectal tumorigenesis through the activation of ras-mapk pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5177caa898a641d98b6a15973fb91965
work_keys_str_mv	AT hongchiehtsai acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT hanhsingtsou acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT chunchilin acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT shaochenchen acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT hsiaoweicheng acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT tsungyunliu acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT weishonechen acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT jengkaijiang acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT shunghauryang acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT shihchingchang acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT haoweiteng acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway AT hsiangtsaiwang acroleincontributestohumancolorectaltumorigenesisthroughtheactivationofrasmapkpathway
_version_	1718379704041340928

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

Ejemplares similares