Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells

Cell Death & Disease
Tae Woo KimSeong-Gyu Ko

Abstract

Kaempferol, a flavonoid, found in traditional medicine, fruits, and vegetables, and an HDAC inhibitor, is a powerful anti-cancer reagent against various cancer cell lines. However, detailed mechanisms involved in the treatment of gastric cancer (GC) using kaempferol are not fully understood. In our study, we investigated the biological activity and molecular mechanism involved in kaempferol-mediated treatment of GC. Kaempferol promoted autophagy and cell death, and increased LC3-I to LC3-II conversion and the downregulation of p62 in GC. Furthermore, our results showed that kaempferol induces autophagic cell death via the activation of the IRE1-JNK-CHOP signaling, indicating ER stress response. Indeed, the inhibition of ER stress suppressed kaempferol-induced autophagy and conferred prolonged cell survival, indicating autophagic cell death. We further showed that kaempferol mediates epigenetic change via the inhibition of G9a (HDAC/G9a axis) and also activates autophagic cell death. Taken together, our findings indicate that kaempferol activates the IRE1-JNK-CHOP signaling from cytosol to nucleus, and G9a inhibition activates autophagic cell death in GC cells.

References

Jan 1, 1966·Annual Review of Physiology·C De Duve, R Wattiaux
Aug 13, 2005·International Journal of Food Sciences and Nutrition·Monika BajpaiDhan Prakash
Sep 6, 2006·EMBO Reports·Eva SzegezdiAfshin Samali
Oct 13, 2006·Molecular and Cellular Biology·Maiko OgataKazunori Imaizumi
Aug 25, 2007·Nature Reviews. Molecular Cell Biology·M Chiara MaiuriGuido Kroemer
Jun 24, 2008·Molecular Cell·Yongjie WeiBeth Levine
Aug 17, 2011·Journal of Biomedical Science·Ke ChenZhao-hui Mo
Jan 20, 2012·Experimental & Molecular Medicine·Kyeong Sook Choi
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Noor GammohXuejun Jiang
Jun 16, 2012·Journal of Biomedicine & Biotechnology·Chung Heon RyuSin-Soo Jeun
Nov 20, 2012·The Journal of Nutritional Biochemistry·Alexander BergerMichael Bitzer
May 21, 2013·Nature Cell Biology·Ryan C RussellKun-Liang Guan
Jul 3, 2013·Seminars in Cancer Biology·Séverine LorinPatrice Codogno
Aug 7, 2013·Molecular and Cellular Biology·Amaia Artal-Martinez de NarvajasDaniel D Billadeau
Aug 28, 2013·Molecular and Cellular Biology·Patrick L Collins, Eugene M Oltz
Sep 3, 2013·Biochimica Et Biophysica Acta·Ana Catarina R G FonsecaCláudia F Pereira
Aug 29, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michelle CicchiniBing Xia
Dec 17, 2014·Oncology Reports·Haibin SongYingwei Xue
Jan 31, 2015·Acta Biochimica Et Biophysica Sinica·Yiming LiZhinan Chen
Jan 31, 2015·Biochemical and Biophysical Research Communications·Aishu RenGang Fu
Jul 24, 2015·Journal of Pineal Research·Anna FernándezJosé L Mauriz
Oct 7, 2015·Frontiers in Immunology·Francesco CascielloJason S Lee
May 14, 2016·Nature Communications·Zhenhua XuJ Alan Diehl
Oct 11, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Imran KhanSun Chul Kang

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Citations

Nov 15, 2018·International Journal of Molecular Sciences·Salvatore ChirumboloTaras Upyr
May 2, 2019·Molecular Carcinogenesis·Fiona ChalmersAdam B Glick
May 2, 2019·Molecular Reproduction and Development·Amira Abdalla Abdelshafy MohamedYaping Jin
May 18, 2019·Clinical Epigenetics·Shizhao LiTrygve O Tollefsbol
Sep 22, 2019·International Journal of Molecular Sciences·Itika AroraTrygve O Tollefsbol
Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chao YinHongjuan Cui
Oct 17, 2019·International Journal of Molecular Sciences·Sudip DhakalIan Macreadie
Dec 13, 2019·Phytotherapy Research : PTR·Milad AshrafizadehSaeed Samarghandian
Jun 28, 2019·Frontiers in Oncology·Qingmei YeRen-Wang Jiang
Jun 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Muhammad ImranLeticia M Estevinho
Sep 8, 2019·International Journal of Molecular Sciences·Natalia SiweckaIreneusz Majsterek
Jan 23, 2020·International Journal of Molecular Sciences·Qian-Qian MaoHua-Bin Li
May 19, 2019·International Journal of Molecular Sciences·Hee-Sung ChaeHyungshin Yim
Sep 29, 2019·DNA and Cell Biology·Hangqi LiuMing Su
Aug 6, 2020·International Journal of Molecular Sciences·Matteo CanaleMatías A Avila
Sep 16, 2020·International Journal of Molecular Sciences·Monica BenvenutoRoberto Bei
Oct 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Seung Wan SonJong Kook Park
Nov 26, 2020·Cancers·Valdenizia R SilvaDaniel P Bezerra
Dec 30, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Nirmalya Saha, Andrew G Muntean
May 26, 2020·Seminars in Cancer Biology·Srimanta PatraSujit K Bhutia
Jan 25, 2021·Ecotoxicology and Environmental Safety·Yang YangFuqin Li
Oct 30, 2020·International Journal of Molecular Sciences·Polina V ShnaiderVictoria O Shender
Nov 17, 2020·Frontiers in Oncology·Jose G Alvarez-MeythalerMatilde E LLeonart
Feb 7, 2021·International Journal of Molecular Sciences·Junyan QuZhenghong Lin
Mar 6, 2021·Journal of Agricultural and Food Chemistry·Haili WuZhuoyu Li
Mar 27, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Francesca Manuela Johnson de Sousa BritoAnna Daroszewska
Oct 9, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Mengdie LuoJonathan D Smith
Mar 9, 2021·Immunology·Mario Riera Romo
May 13, 2021·International Journal of General Medicine·Ting XiuFan-Bo Jing

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Methods Mentioned

BETA
co-immunoprecipitation
immunoprecipitation
lipidation
transfection
ChIP
ELISA
Protein Assay
PCR
confocal microscopy
pull down

Software Mentioned

CellSignaling

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