Corilagin induces pyroptosis in AML cells by activating the TXNIP-caspase-3-GSDME pathway.

[UNLABELLED] Acute myeloid leukemia (AML) is a hematological malignancy characterized by clonal expansion of myeloid progenitors in the bone marrow, resulting in impaired hematopoiesis. AML remains challenging due to frequent disease recurrence and limited treatment alternatives, highlighting the necessity for further research. Corilagin, an ellagitannin isolated from ethnopharmacological plants, displays potential anti-cancer activity, but its anti-leukemic effects and mechanism in AML are unclear. This study aimed to assess whether corilagin induces cell death in AML cells, a cell-derived xenograft (CDX) model, and primary AML cells, and to elucidate its therapeutic mechanism in AML. Cell viability was measured using the Cell Counting Kit-8 and proliferation was assessed with an EdU imaging kit. Flow cytometry analyzed PI-positive cells. Pyroptosis was evaluated by morphology and LDH release. mRNA and protein levels were measured by qPCR and western blot. Stable cell lines with gene knockouts were created using CRISPR-Cas9. The therapeutic efficacy of corilagin was also tested in CDX models. Corilagin treatment induced pyroptotic bubbles in AML cells, increasing LDH release and PI-positive cells. Corilagin activated caspase-3, which cleaved gasdermin E (GSDME) to form active GSDME-NT, promoting pyroptosis. Corilagin also activated thioredoxin-interacting protein (TXNIP), and TXNIP knockdown by siRNA rescued corilagin-induced pyroptosis. Corilagin reduced viability and promoted pyroptosis in primary AML cells. In an AML CDX mouse model, corilagin inhibited leukemia progression and prolonged survival. Our results suggested that corilagin induced pyroptosis in AML by activating the TXNIP/caspase-3/GSDME pathway, offering a potential therapeutic strategy for AML.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s00277-026-06862-z.