title: Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome.
abstract: Paclitaxel is generally used to treat cancers in clinic as an inhibitor of cell division. However, the acquired resistance in tumours limits its clinical efficacy. Therefore, the aim of this study was to detect whether co-treatment with lentinan enhanced the anti-cancer effects of paclitaxel in A549 cells. We found that the combination of paclitaxel and lentinan resulted in a significantly stronger inhibition on A549 cell proliferation than paclitaxel treatment alone. Co-treatment with paclitaxel and lentinan enhanced cell apoptosis rate by inducing caspase-3 activation. Furthermore, co-treatment with paclitaxel and lentinan significantly triggered reactive oxygen species (ROS) production, and increased thioredoxin-interacting protein (TXNIP) expression. Moreover, co-treatment with paclitaxel and lentinan enhanced TXNIP-NLRP3 interaction, and activated NLRP3 inflammasome whereat interleukin-1β levels were increased and cell apoptosis was induced. In addition, combination of paclitaxel and lentinan could activate apoptosis signal regulating kinase-1 (ASK1)/p38 mitogen-activated protein kinase (MAPK) signal which also contributed to cell apoptosis. Taken together, co-treatment with paclitaxel and lentinan exerts synergistic apoptotic effects in A549 cells through inducing ROS production, and activating NLRP3 inflammasome and ASK1/p38 MAPK signal pathway.
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Wei
authors: W
authors: Liu
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Jun
authors: J
authors: Gu
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Jun
authors: J
authors: Qi
authors: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Xiao-Ning
authors: XN
authors: Zeng
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Juan
authors: J
authors: Ji
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Zheng-Zhen
authors: ZZ
authors: Chen
authors: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Xiu-Lan
authors: XL
authors: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007912:Lentinan / Q000494:pharmacology*; D048848:MAP Kinase Kinase Kinase 5; D008954:Models, Biological; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; C486715:TXNIP protein, human; D007912:Lentinan; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D053148:Caspase 3; D017239:Paclitaxel
keywords: NLRP3; ROS; TXNIP; lentinan; paclitaxel