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Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway

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Author(s)
Kyoung Ah KangMei Jing PiaoSusara Ruwan Kumara Madduma HewageYea Seong RyuMin Chang OhTaeg Kyu KwonSungwook ChaeJin Won Hyun
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Tumour Biology
Issued Date
2016
Volume
37
Issue
7
Keyword
FisetinHuman non-small cell lung cancerApoptosisReactive oxygen speciesER stressMAPK signaling pathway
Abstract
Fisetin (3,3′,4′,7-tetrahydroxyflavone), a dietary flavonoid compound, is currently being investigated for its anticancer effect in various cancer models, including lung cancer. Recent studies show that fisetin induces cell growth inhibition and apoptosis in the human non-small cell lung cancer line NCI-H460. In this study, we investigated whether fisetin can induce endoplasmic reticulum (ER) stress-mediated apoptosis in NCI-H460 cells. Fisetin induced mitochondrial reactive oxygen species (ROS) and characteristic signs of ER stress: ER staining; mitochondrial Ca2+ overload; expression of ER stress-related proteins; glucose-regulated protein (GRP)-78, phosphorylation of protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylation of eukaryotic initiation factor-2 α subunit; cleavage of activating transcription factor-6; phosphorylation of inositol-requiring kinase-1 and splicing of X-box transcription factor-1; induction of C/EBP homologous protein and cleaved caspase-12. siRNA-mediated knockdown of CHOP and ATF-6 attenuated fisetin-induced apoptotic cell death. In addition, fisetin induced phosphorylation of ERK, JNK, and p38 MAPK. Moreover, silencing of the MAPK signaling pathway prevented apoptotic cell death. In summary, our results indicate that, in NCI-H460 cells, fisetin induces apoptosis and ER stress that is mediated by induction of the MAPK signaling pathway.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Kyoung Ah Kang et al. (2016). Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway. Tumour Biology, 37(7), 9615–9624.
Type
Article
ISSN
1010-4283
Source
https://link.springer.com/article/10.1007/s13277-016-4864-x
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32710
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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