Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS‐TXNIP‐NLRP3 inflammasome

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...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2015-08, Vol.19 (8), p.1949-1955
Main Authors: Liu, Wei, Gu, Jun, Qi, Jun, Zeng, Xiao‐Ning, Ji, Juan, Chen, Zheng‐Zhen, Sun, Xiu‐Lan
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Carrier Proteins - metabolism
Caspase 3 - metabolism
Cell Line, Tumor
Cell Proliferation - drug effects
Drug Synergism
Enzyme Activation - drug effects
Humans
Inflammasomes - metabolism
lentinan
Lentinan - pharmacology
MAP Kinase Kinase Kinase 5
Models, Biological
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3
Original
p38 Mitogen-Activated Protein Kinases - metabolism
paclitaxel
Paclitaxel - pharmacology
Phosphorylation - drug effects
Protein Binding - drug effects
Reactive Oxygen Species - metabolism
ROS
Time Factors
TXNIP
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Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.12570