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Publication Detail

Title: Arsenic-induced apoptosis in the p53-proficient and p53-deficient cells through differential modulation of NFkB pathway.

Authors: Yin, Lei; Yu, Xiaozhong

Published In Food Chem Toxicol, (2018 Aug)

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 p53-/- cells to examine the NFκB pathway and proinflammatory cytokines after arsenic treatment. Arsenic reduced cell viability and increased more apoptosis in the p53-/- 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 p53-/- 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 p53-/- 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 p53-/- cells and this observation of the differential mechanism of cell death between the p53+/+ and p53-/- cells might be linked to the unique ability of arsenic to act as both a carcinogen and a chemotherapeutic agent.

PubMed ID: 29944914 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis/drug effects*; Arsenic/toxicity*; Cells, Cultured; Cytokines/metabolism; Gene Expression Profiling; Gene Regulatory Networks; Genotype; Inflammation Mediators/metabolism; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases/metabolism; NF-kappa B/metabolism*; Transcription Factors/metabolism; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism*

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