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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-06-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-92035-z |
| _version_ | 1818436477901602816 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T17:09:24Z |
| format | Article |
| id | doaj.art-5177caa898a641d98b6a15973fb91965 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T17:09:24Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5177caa898a641d98b6a15973fb919652022-12-21T22:53:38ZengNature PortfolioScientific Reports2045-23222021-06-0111111310.1038/s41598-021-92035-zAcrolein contributes to human colorectal tumorigenesis through the activation of RAS-MAPK pathwayHong-Chieh Tsai0Han-Hsing Tsou1Chun-Chi Lin2Shao-Chen Chen3Hsiao-Wei Cheng4Tsung-Yun Liu5Wei-Shone Chen6Jeng-Kai Jiang7Shung-Haur Yang8Shih-Ching Chang9Hao-Wei Teng10Hsiang-Tsai Wang11Department of Neurosurgery, Linkou Chang Gung Memorial HospitalInstitute of Food Safety and Health Risk Assessment, National Yang-Ming UniversitySchool of Medicine, National Yang-Ming UniversityInstitute of Food Safety and Health Risk Assessment, National Yang-Ming UniversityInstitute of Pharmacology, College of Medicine, National Yang-Ming UniversityInstitute of Food Safety and Health Risk Assessment, National Yang-Ming UniversitySchool of Medicine, National Yang-Ming UniversitySchool of Medicine, National Yang-Ming UniversitySchool of Medicine, National Yang-Ming UniversitySchool of Medicine, National Yang-Ming UniversitySchool of Medicine, National Yang-Ming UniversityInstitute of Pharmacology, College of Medicine, National Yang-Ming UniversityAbstract 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.https://doi.org/10.1038/s41598-021-92035-z |
| spellingShingle | 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 Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-021-92035-z |
| 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 |