Yulian Liu , Mengyue Fan , Yuanxin Chen , Chuanmin Zhang , Lijuan Wang , Yao Fu
{"title":"Polyphyllin I通过激活caspase-6/ZBP1/NLRP3信号通路诱导弥漫性大b细胞淋巴瘤的焦亡。","authors":"Yulian Liu , Mengyue Fan , Yuanxin Chen , Chuanmin Zhang , Lijuan Wang , Yao Fu","doi":"10.1016/j.intimp.2025.115592","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115592"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Polyphyllin I induces pyroptosis in diffuse large B-cell lymphoma by activating the caspase-6/ZBP1/NLRP3 signaling pathway\",\"authors\":\"Yulian Liu , Mengyue Fan , Yuanxin Chen , Chuanmin Zhang , Lijuan Wang , Yao Fu\",\"doi\":\"10.1016/j.intimp.2025.115592\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":13859,\"journal\":{\"name\":\"International immunopharmacology\",\"volume\":\"166 \",\"pages\":\"Article 115592\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International immunopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1567576925015838\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925015838","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.