Polyphyllin I induces pyroptosis in diffuse large B-cell lymphoma by activating the caspase-6/ZBP1/NLRP3 signaling pathway.

Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive and heterogeneous hematological malignancy of B-cell origin, commonly observe in clinical practice. Chemotherapy resistance poses a significant challenge to DLBCL treatment, necessitating novel therapies. Polyphyllin I (PPI) exhibits anticancer effects on various cancer cells, but its impact on DLBCL remains unclear. This study investigated the mechanism underlying PPI in treating DLBCL, specifically focusing on the caspase-6/ZBP1/NLRP3 pathway involved in pyroptosis and apoptosis. The role caspase-6 plays in regulating pyroptosis is unknown. We hypothesized PPI activates this pathway, triggering tumor cell death. Through both in vitro and in vivo experiments, we found that PPI significantly promoted DLBCL cell pyroptosis and apoptosis by activating the caspase-6/ZBP1/NLRP3 pathway. These findings suggest that the caspase-6 pathway has the potential to be developed as a novel treatment for DLBCL. Further research is needed to explore the clinical application of PPI in lymphoma treatment and its potential synergies with other drugs.