Open AccessLentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS ‐ TXNIP ‐ NLRP 3 inflammasome
Author(s) -
Liu Wei,
Gu Jun,
Qi Jun,
Zeng XiaoNing,
Ji Juan,
Chen ZhengZhen,
Sun XiuLan
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12570
Subject(s) - lentinan , txnip , paclitaxel , apoptosis , a549 cell , inflammasome , chemistry , mapk/erk pathway , pharmacology , cancer research , microbiology and biotechnology , signal transduction , medicine , biology , biochemistry , oxidative stress , cancer , thioredoxin , receptor , polysaccharide
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 ‐ NLRP 3 interaction, and activated NLRP 3 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 ( ASK 1)/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 NLRP 3 inflammasome and ASK 1/p38 MAPK signal pathway.