Contribution of the ROS/IRE1α Signaling Pathway to Arsenic Trioxide-Induced Apoptosis and Autophagy-Associated Responses in BEAS-2B Cells

Inorganic arsenic primarily originates from geological processes and human activities. Exposure to high concentrations of inorganic arsenic can cause diverse health problems, with lung injury being one of the main hazards. The present study sought to elucidate the cytotoxicity and underlying mechanisms of inorganic arsenic in BEAS-2B cells. The results showed that exposure of BEAS-2B cells to arsenic trioxide (As2O3) for 24 h resulted in a dose-dependent decline in viability. As2O3 triggered reactive oxygen species (ROS) production in BEAS-2B cells, and ROS contributed to increased p-IRE1α and p-eIF2α abundance relative to β-actin, along with GRP78 protein expression. The autophagy-associated and apoptotic responses induced by As2O3 in BEAS-2B cells were likewise associated with ROS. Further analysis revealed that increased p-IRE1α abundance relative to β-actin is involved in As2O3-triggered autophagy-associated responses and apoptosis in BEAS-2B cells. The antioxidant N-acetylcysteine (NAC) markedly attenuated As2O3-induced apoptosis and autophagy-associated responses and reduced p-IRE1α abundance relative to β-actin. Collectively, these findings indicate that the ROS/IRE1α pathway contributes to As2O3-triggered autophagy-associated responses and apoptosis in BEAS-2B cells.