Investigation of the effect of paraoxonase-1 (PON1) enzyme on MAPK signaling pathway in colon cancer cells

As one of the most problematic challenges in the world colorectal carcinomas are among the five leading and most common malignancies of the gastrointestinal tract worldwide and in Turkey. From a molecular point of view, the biological role of reactive oxygen species in cancer signaling has been demonstrated. Not only in the initiation of colon carcinogenesis, but ROS also plays a crucial role in the progression of colon carcinogenesis. Nowadays, PON 1 is recognized as an effective antioxidant, which is considered a radical scavenger in the human body. Therefore, it seems that a comprehensive understanding of the role of these PON enzymatic activities may play an important role in the etiology and prevention of many cancers. Moreover, molecular studies have revealed that the MAPK signaling pathway is overactivated in approximately one-third of human tumors. Therefore, the enzymatic activities of PON1 and MAPK signaling pathways in colorectal cancer will be investigated to determine whether they may hold promise for novel diagnostic or therapeutic applications in colorectal cancer. In this study, HT -29 colon cancer cell lines and the CCD-18Co healthy colon cell lines were used. The enzymatic activities of PON1 were determined using a spectrophotometer. B-Raf, p-B-Raf, ERK, and p- ERK proteins involved in MAPK signaling pathways amd serum levels of PON1 were detected and analyzed by the Western blotting method. Moreover, we found that PON1 level and PON1 enzyme activity were significantly decreased in HT -29 cells compared with CCD-18Co cells (p=0.0173, p=0.0281, respectively). Also, we found that the levels of p-B-Raf and p- ERK, which activate the MAPK signaling pathway, were significantly increased in HT -29 cells (p=0.0037, p=0.0074, respectively). According to our results, a positive correlation was found between the PON1 level and PON1 enzyme activity (p=0.008). Moreover, a negative correlation was found between PON1 level and p-B-Raf/p-ERK protein levels, which play a role in the MAPK pathway (p=0.016, 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, p=0.037, respectively). In a conclusion, it is thought that the increasing levels of the proteins involved in the MAPK signaling pathway in cancerous cells are caused by the decreasing serum levels of PON1, and enzymatic activities of PON1.