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

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...

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Autores principales: Kim, Tae Woo, Lee, Seon Young, Kim, Mia, Cheon, Chunhoo, Ko, Seong-Gyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115440/
https://www.ncbi.nlm.nih.gov/pubmed/30158521
http://dx.doi.org/10.1038/s41419-018-0930-1
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author Kim, Tae Woo
Lee, Seon Young
Kim, Mia
Cheon, Chunhoo
Ko, Seong-Gyu
author_facet Kim, Tae Woo
Lee, Seon Young
Kim, Mia
Cheon, Chunhoo
Ko, Seong-Gyu
author_sort Kim, Tae Woo
collection PubMed
description 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.
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spelling pubmed-61154402018-08-30 Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells Kim, Tae Woo Lee, Seon Young Kim, Mia Cheon, Chunhoo Ko, Seong-Gyu Cell Death Dis Article 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. Nature Publishing Group UK 2018-08-29 /pmc/articles/PMC6115440/ /pubmed/30158521 http://dx.doi.org/10.1038/s41419-018-0930-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Tae Woo
Lee, Seon Young
Kim, Mia
Cheon, Chunhoo
Ko, Seong-Gyu
Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells
title Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells
title_full Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells
title_fullStr Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells
title_full_unstemmed Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells
title_short Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells
title_sort kaempferol induces autophagic cell death via ire1-jnk-chop pathway and inhibition of g9a in gastric cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115440/
https://www.ncbi.nlm.nih.gov/pubmed/30158521
http://dx.doi.org/10.1038/s41419-018-0930-1
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