Suppression of Stress Granule Assembly Sensitizes SH-SY5Y Cells to Hexachlorophene-Induced Cellular Toxicity

Hexachlorophene is a topical antiseptic historically used for skin cleansing and preoperative skin disinfection, but its use today is tightly restricted due to neurotoxicity risks. However, its underlying mechanisms are still not fully understood. Here, we investigated hexachlorophene-induced stress responses and cell death pathways in human neuroblastoma SH-SY5Y cells. Hexachlorophene treatment induced G3BP stress granule assembly factor 1 (G3BP1)–positive stress granules (SGs) in a time- and dose-dependent manner, along with increased eIF2α phosphorylation at serine 51, indicating activation of canonical translational repression. In addition, inhibition of G3BP1 using the selective inhibitor FAZ-3532 effectively suppressed SG formation but worsened hexachlorophene-induced cytotoxicity, suggesting that SGs serve a protective function under chemical stress. Despite SG suppression, eIF2α phosphorylation remained elevated. Collectively, these results demonstrate that SGs are adaptively formed in response to hexachlorophene and act to mitigate neuronal toxicity. Disruption of SG assembly sensitizes neuronal cells to stress, and the enhanced cytotoxicity was mediated through apoptosis, highlighting the functional importance of SGs in hexachlorophene mediated neurotoxic contexts.