Arsenic trioxide induces gasdermin E mediated pyroptosis in astroglioma cells

Background: Arsenic trioxide (ATO) has been proved useful for the treatment of acute promyelocytic leukemia (APL). Apoptosis is the result of the cytotoxic effect of ATO, apoptotic mediated cell death confirmed by DNA fragmentation and Annexin V staining. Although signaling associated with ATO-induced apoptosis has been well defined, it is still unknown whether other forms of cell death are involved in ATO-induced cell death. Methods: Western blotting, cytotoxicity assay, transmission electron microscopy were used to evaluate other forms of cell death in U251 cells. Results: We found that pyroptotic mediated cell death was observed in U251 cells after ATO treatment, which was confirmed by observing the increased gasdermin E (GSDME) cleavage, lactate dehydrogenase (LDH) release and transmission electron microscopy imaging. Consistent with previous results, caspase-3 was activated by ATO, which was also important for GSDME cleavage and subsequent pyroptosis. Conclusions: We reported that GSDME mediated pyroptosis involved in ATO induced cell death in astroglioma cells.