Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8547230 | Food and Chemical Toxicology | 2018 | 47 Pages |
Abstract
Arsenic is a well-known environmental carcinogen and an effective chemotherapeutic agent. The underlying mechanism of this dual-effect, however, is not fully understood. In this study, we applied mouse p53+/+ and p53â/â cells to examine the NFκB pathway and proinflammatory cytokines after arsenic treatment. Arsenic reduced cell viability and increased more apoptosis in the p53â/â cells as compared to p53+/+ cells, which was correlated with activation of SAPK/JNK, p38 MAPK, and AKT pathways. A transcriptional regulatory network analysis revealed that arsenic activated transcription regulatory elements E2F, Egr1, Trp53, Stat6, Bcl6, Creb2 and ATF4 in the p53+/+ cells, while in the p53â/â cells, arsenic treatment altered transcription factors NFκB, Pparg, Creb2, ATF4, and Egr1. We observed dynamic changes in phosphorylated NFκB p65 (p-NFκB p65) and phosphorylated IKKαβ (p-IKKαβ) in both genotypes from 4 h to 24 h after treatment, significant decreases of p-NFκB p65 and p-IKKαβ in the p53â/â cells, whereas increases of p-NFκB p65 and p-IKKαβ were observed in the p53+/+ cells. Our study confirmed the differential modulation of NFκB pathway by arsenic in the p53+/+ or p53â/â cells and this observation of the differential mechanism of cell death between the p53+/+ and p53â/â cells might be linked to the unique ability of arsenic to act as both a carcinogen and a chemotherapeutic agent.
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Authors
Lei Yin, Xiaozhong Yu,