Schematic illustration of the principal signaling pathways that are affected by sodium arsenite (As) treatment

A schematic illustration of the principal signaling pathways that are affected by sodium arsenite (As) treatment. Arsenite accelerates activation of the MAPK pathways at the EGFR that finally up-regulates MAPK p38, ERK and JNK and the correspondent transcription factors of the AP-1 family: ATF2, c-Fos, c-Jun. Arsenite suppresses the JAK2-STAT3 and IKK-NF-κB signaling pathways and down-regulates expression of STAT3- and NF-κB-dependent anti-apoptotic genes. The third direction of the arsenic effects is linked with Rac1-NADPH oxidase activation, production ROS (superoxide), induction oxidative and genotoxic stress and initiation of the mitochondrial death pathway in some melanoma lines. At low doses (1–10 μM), arsenite preferentially plays a role of the regulator of cell signaling and gene expression, inducing expression and translocation to the cell surface TRAIL and its Receptor-1 and Receptor-2. This creates conditions for an induction of the TRAIL-mediated death pathway via paracrine mechanism and dramatically increases a susceptibility of arsenite-treated cells to the exogenous TRAIL. See additional explanation and references in the text.

Publication

Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression. () Vladimir N. Ivanov, et al. Exp Cell Res. ;312(20):4120-4138. Figure: F9. All organisms Mus musculus Homo sapiens Drosophila melanogaster

Disease mentions