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

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kyoung Ah KangJin Won Hyun

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 Ca(2+) 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...Continue Reading

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Citations

Aug 3, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kyoung-Jin MinTaeg Kyu Kwon
Apr 21, 2018·Journal of Cellular and Molecular Medicine·Li LinJian-Zhi Wang
May 9, 2019·Biomolecules·Dharambir KashyapSardul Singh Sandhu
Apr 9, 2020·Experimental and Therapeutic Medicine·Lihui LongHonglin Yan
Feb 25, 2020·Current Topics in Medicinal Chemistry·Muhammad Shoaib Ali GillNafees Ahemad
Apr 3, 2019·Journal of Clinical Biochemistry and Nutrition·Dong-Hoon WonSung-Dae Cho
Nov 2, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jerry D MonroeMichael E Smith
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Jan 2, 2019·Cancers·Mariam AbotalebDietrich Büsselberg
Feb 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Huihui ZhangJihua Chen
May 16, 2020·Scientific Reports·Jin-Woo LeeKyung Sook Kim
Jan 22, 2021·Food Science & Nutrition·Muhammad ImranFaqir M Anjum
Jul 31, 2021·Bioorganic Chemistry·Vikram Jeet SinghPooja A Chawla

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