Modulation of arsenic-induced epidermal growth factor receptor pathway signalling by resveratrol.

摘要: Arsenic (As) is both a human carcinogen and an effective anticancer drug. These aspects of arsenic toxicity develop as consequence arsenic-induced oxidative stress modifications to signal pathway activity which alter gene expression. Resveratrol (RVL) food antioxidant found in grapes other fruits, exhibits anti-carcinogenic properties by reducing restoring control. This study investigated the impact RVL on arsenite [As(III)]-induced cell signalling HaCaT keratinocytes assaying phosphorylation status epidermal growth factor receptor (EGFR) intermediates measuring changes expression Phase II DNA repair biomarkers. As(III) exposure produced dose-dependent was associated with increased activation EGFR intermediates, cSrc, Rac1 extracellular signal-regulated kinases 1 2 (ERK1/2). Arsenic-mediated ERK1/2 negatively regulated polymerase beta up heme-oxygenase-1 at toxic concentrations. treatment modulated As(III)-mediated shifting balance cSrc regulatory domain phosphorylation. effects significantly altered response factor-induced stimulation. Our research provides evidence that pharmacologically relevant doses influences cellular responses As(III), largely due RVL-mediated Src activation.