Fumonisin B1 triggers carcinogenesis via HDAC/PI3K/Akt signalling pathway in human esophageal epithelial cells.

Fumonisin B1 (FB1) is a contaminant that commonly present in the global environment, especially in food and feed. Epidemiologic studies have shown that esophageal cancer is associated with fumonisin toxicity. However, the molecular mechanism of FB1-induced esophageal cancer is unclear. In this research, the molecular mechanism of FB1-induced cell carcinogenesis in human esophageal epithelial cells line (HEEC) was explored. We found that FB1 (0.3125-5 μM) could promote cell proliferation, and the same phenomenon was found in a 3D cell model. FB1 could also accelerate cell migration. The expression levels of DNA damage markers were significantly increased after FB1 exposure. Meanwhile, the expression levels of cell cycle-regulated proteins and cancer-related genes were abnormal. Furthermore, FB1 significantly upregulated the histone deacetylase (HDAC) expression and activated the phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signalling pathway. The HDAC inhibitor trichostatin A (TSA) could repressed FB1-promoted cell proliferation and abnormal phenomenon induced by FB1. Moreover, myriocin (ISP-1) could relieve FB1-enhanced HDAC expression and cell proliferation, which implied that ISP-1 may be used to block the fumonisin toxicity in the future. Our findings suggested that the HDAC/PI3K/Akt signalling pathway is a novel mechanism for FB1-induced cell carcinogenesis in HEEC and provided new ideas for the prevention and control of fumonisin toxicity, subsequently avoiding adverse effects on the ecosystem and human health.