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Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells
Pyroptosis is related to the occurrence, development, and therapeutic response of tumors, mediated by the proteins of the Gasdermin family. These proteins have become potential biomarkers for cancer treatment, and their agonists are likely to become a new direction in research and development of ant...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458876/ https://www.ncbi.nlm.nih.gov/pubmed/36091790 http://dx.doi.org/10.3389/fphar.2022.959938 |
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author | Han, Jicheng Cheng, Cheng Zhang, Jinxin Fang, Jinbo Yao, Wei Zhu, Yilong Xiu, Zhiru Jin, Ningyi Lu, Huijun Li, Xiao Li, Yiquan |
author_facet | Han, Jicheng Cheng, Cheng Zhang, Jinxin Fang, Jinbo Yao, Wei Zhu, Yilong Xiu, Zhiru Jin, Ningyi Lu, Huijun Li, Xiao Li, Yiquan |
author_sort | Han, Jicheng |
collection | PubMed |
description | Pyroptosis is related to the occurrence, development, and therapeutic response of tumors, mediated by the proteins of the Gasdermin family. These proteins have become potential biomarkers for cancer treatment, and their agonists are likely to become a new direction in research and development of antitumor drugs. In this study, we found that myricetin has an inhibitory effect on lung cancer cells of the activation of pyroptosis. Analysis of the expression of Gasdermin family proteins revealed that this phenomenon was caused by the cleavage of GSDME. Subsequently, specific inhibitors, we found that caspase-3 was its upstream activation factor. In addition, mitochondrial and endoplasmic reticulum (ER) analysis showed that myricetin can cause endoplasmic reticulum stress and increase reactive oxygen species (ROS) levels. Subsequent inhibition of caspase-12 revealed that the expression levels of cleaved-caspase-3 and cleaved-GSDME were significantly reduced, resulting in the inhibition of pyroptosis. Using in vivo experiments, we also found that the treatment with myricetin can reduce tumor volume and significantly increase the level of pyroptosis-related proteins in tumor tissues. Overall, our findings show that myricetin induces cell death of lung cancer cells primarily through an ER stress pathway-induced pyroptosis. Therefore, myricetin has the potential to be used as a pyroptosis agonist in research and development of antitumor drugs. |
format | Online Article Text |
id | pubmed-9458876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94588762022-09-10 Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells Han, Jicheng Cheng, Cheng Zhang, Jinxin Fang, Jinbo Yao, Wei Zhu, Yilong Xiu, Zhiru Jin, Ningyi Lu, Huijun Li, Xiao Li, Yiquan Front Pharmacol Pharmacology Pyroptosis is related to the occurrence, development, and therapeutic response of tumors, mediated by the proteins of the Gasdermin family. These proteins have become potential biomarkers for cancer treatment, and their agonists are likely to become a new direction in research and development of antitumor drugs. In this study, we found that myricetin has an inhibitory effect on lung cancer cells of the activation of pyroptosis. Analysis of the expression of Gasdermin family proteins revealed that this phenomenon was caused by the cleavage of GSDME. Subsequently, specific inhibitors, we found that caspase-3 was its upstream activation factor. In addition, mitochondrial and endoplasmic reticulum (ER) analysis showed that myricetin can cause endoplasmic reticulum stress and increase reactive oxygen species (ROS) levels. Subsequent inhibition of caspase-12 revealed that the expression levels of cleaved-caspase-3 and cleaved-GSDME were significantly reduced, resulting in the inhibition of pyroptosis. Using in vivo experiments, we also found that the treatment with myricetin can reduce tumor volume and significantly increase the level of pyroptosis-related proteins in tumor tissues. Overall, our findings show that myricetin induces cell death of lung cancer cells primarily through an ER stress pathway-induced pyroptosis. Therefore, myricetin has the potential to be used as a pyroptosis agonist in research and development of antitumor drugs. Frontiers Media S.A. 2022-08-26 /pmc/articles/PMC9458876/ /pubmed/36091790 http://dx.doi.org/10.3389/fphar.2022.959938 Text en Copyright © 2022 Han, Cheng, Zhang, Fang, Yao, Zhu, Xiu, Jin, Lu, Li and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Han, Jicheng Cheng, Cheng Zhang, Jinxin Fang, Jinbo Yao, Wei Zhu, Yilong Xiu, Zhiru Jin, Ningyi Lu, Huijun Li, Xiao Li, Yiquan Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells |
title | Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells |
title_full | Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells |
title_fullStr | Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells |
title_full_unstemmed | Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells |
title_short | Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells |
title_sort | myricetin activates the caspase-3/gsdme pathway via er stress induction of pyroptosis in lung cancer cells |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458876/ https://www.ncbi.nlm.nih.gov/pubmed/36091790 http://dx.doi.org/10.3389/fphar.2022.959938 |
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