Arsenic trioxide induces gasdermin E mediated pyroptosis in astroglioma cells

Arsenic trioxide (ATO) has been considered as an anticancer activity in various malignancies with a large body of mechanisms. In acute promyelocytic leukemia (APL), ATO is an effective therapeutic intervention to improve the patients’ survival and remission (1). ATO could induce the degradation of PML-RARα to result in terminal differentiation and apoptosis which may result from the Bcl-2 downregulation and cytochrome c release (2). Recently, ATO was applied to the treatment of non-small cell lung cancer (NSCLC) by inducing cell cycle arrest (3). Moreover, ATO could trigger DNA damage and apoptosis in glioma cells (4,5). Pyroptosis is a pro-inflammatory form of programmed cell death against pathogen infection, which is critical for the antimicrobial response (6). Prior results suggested pyroptosis was mainly observed in myeloid cells (7). Recent attention on the role of pyroptosis as a programmed cell death suggested that gasdermin E (GSDME)-mediated pyroptosis contributed to the toxicity of chemotherapy (8). Chemotherapy drugs could cause cancer cell cytotoxicity by activating caspase-3-mediated cleavage of GSMDE (9). More recently, it was reported that iron could activate Original Article