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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number12590
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

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