p-Hydroxylcinnamaldehyde slows the progression of 4NQO-induced oesophageal tumourigenesis via the RhoA-MAPK signaling pathway.
p-Hydroxylcinnamaldehyde isolated from the Cochinchina momordica seed (CMSP) has been identified to inhibit growth and metastasis in oesophageal squamous cell carcinoma (ESCC) by inducing differentiation. The aim of the present study was to evaluate the effect and underlying mechanism of CMSP on 4-nitroquinoline 1-oxide (4NQO)-induced oesophageal tumourigenesis. In the present study, a mouse model of oesophageal preneoplastic lesions was established by providing 4NQO-containing drinking water to C57BL/6 mice. The effect of CMSP on tumourigenesis induced by the chemical mutagen and the effect of CMSP on immune function were investigated. The results showed that the incidence and pathological stage of atypical hyperplasia in oesophageal tissues were significantly reduced in CMSP-treated mice compared with untreated mice. Immunohistochemistry and pull-down assay results revealed that the expression levels of p-ERK1/2, p-SAPK/JNK, and GTP-RhoA were significantly decreased in the oesophageal tissue of CMSP-treated mice. In addition, the proportions of CD4+ T cells, CD8+ T cells, and NK cells were increased, while the proportion of CD4+ CD25+ regulatory T cells (Tregs) was decreased, in the peripheral blood of CMSP-treated mice. These results indicated that CMSP could hamper 4NQO-induced oesophageal tumourigenesis by regulating the RhoA-ERK/JNK signaling pathway and promoting immune system function, thus providing a new potential strategy for treating preneoplastic lesions of the oesophagus.
['Zhao|Lianmei|L|0000-0002-9363-9588', 'Ma|Ming|M|', 'Wu|Hao|H|', 'Zhang|Cong|C|', 'Dai|Suli|S|', 'Dong|Pei|P|', 'Huo|Bingjie|B|', 'Shan|Baoen|B|']
D015112:4-Nitroquinoline-1-oxide D000818:Animals D063646:Carcinogenesis D002934:Cinnamates D018450:Disease Progression D004938:Esophageal Neoplasms D000077277:Esophageal Squamous Cell Carcinoma D004947:Esophagus D020935:MAP Kinase Signaling System D008810:Mice, Inbred C57BL D029775:Momordica D010936:Plant Extracts D011230:Precancerous Conditions D012639:Seeds D020742:rhoA GTP-Binding Protein
oesophageal squamous cell carcinoma (ESCC) preneoplastic lesion immune regulation p-Hydroxylcinnamaldehyde (CMSP)