The attraction of paraoxonase-1 associated with the MAPK pathway on colon carcinoma cells

Abstract

Abstract Objectives A comprehensive understanding of the role of PON enzymatic activities may play an important role in the etiology and prevention of many cancers. PON1 is known as a potent antioxidant that scavenges free radicals in the human body. The enzymatic activities of paraoxonase (PON1) and mitogen-activated protein kinase (MAPK) signalling pathways in colorectal cancer are being investigated to determine whether they hold promise for novel diagnostic or therapeutic applications in colorectal cancer. Methods HT-29 colon cancer cell lines and CCD-18Co colon cell lines were used. B-Raf, p-B-Raf, ERK, and p-ERK proteins involved in MAPK signalling pathways and serum levels of PON1 were detected and analyzed by the Western blotting method. Results The levels and activity of PON1 enzyme were significantly decreased in HT-29 cells compared to CCD-18Co cells (p=0.0173 and p=0.0281, respectively). The levels of p-B-Raf and p-ERK, which activates the MAPK signalling pathway, were significantly increased in HT-29 cells (p=0.0037 and p=0.0074, respectively). Conclusions A positive correlation was found between PON1 level and PON1 enzyme activity (p=0.008). A negative correlation was found between PON1 level and p-B-Raf/p-ERK protein levels, which play a role in the MAPK signalling pathway (p=0.016 and p=0.036, respectively). A negative correlation was also found between PON1 enzyme activity and p-B-Raf/p-ERK protein levels (p=0.060 and p=0.037, respectively). It is suggested that the increase of proteins involved in the MAPK signaling pathway in cancer cells is caused by the decreasing serum levels of PON1 and enzymatic activity of PON1.