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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...

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Autores principales: Han, Jicheng, Cheng, Cheng, Zhang, Jinxin, Fang, Jinbo, Yao, Wei, Zhu, Yilong, Xiu, Zhiru, Jin, Ningyi, Lu, Huijun, Li, Xiao, Li, Yiquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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