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Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis

Liver cancer is a highly lethal malignancy. Despite considerable efforts made in recent years, the prognosis of patients with liver cancer remains poor. Curcuma zedoaria (known as Ezhu in Chinese) is widely prescribed in traditional Chinese medicine. Germacrone (GM) is a sesquiterpene constituent de...

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Autores principales: Sun, Xinfeng, Zhong, Xin, Ma, Wenfeng, Feng, Wenxing, Huang, Qi, Ma, Mengqing, Lv, Minling, Hu, Rui, Han, Zhiyi, Li, Jing, Zhou, Xiaozhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204551/
https://www.ncbi.nlm.nih.gov/pubmed/35747157
http://dx.doi.org/10.3892/etm.2022.11383
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author Sun, Xinfeng
Zhong, Xin
Ma, Wenfeng
Feng, Wenxing
Huang, Qi
Ma, Mengqing
Lv, Minling
Hu, Rui
Han, Zhiyi
Li, Jing
Zhou, Xiaozhou
author_facet Sun, Xinfeng
Zhong, Xin
Ma, Wenfeng
Feng, Wenxing
Huang, Qi
Ma, Mengqing
Lv, Minling
Hu, Rui
Han, Zhiyi
Li, Jing
Zhou, Xiaozhou
author_sort Sun, Xinfeng
collection PubMed
description Liver cancer is a highly lethal malignancy. Despite considerable efforts made in recent years, the prognosis of patients with liver cancer remains poor. Curcuma zedoaria (known as Ezhu in Chinese) is widely prescribed in traditional Chinese medicine. Germacrone (GM) is a sesquiterpene constituent derived from the essential oil of Ezhu, and exerts anti-carcinogenic effects by inducing apoptosis in various cancer cells. The present study investigated the potential mechanism of GM in HepG2 cells. Cell Counting Kit-8, colony-formation and lactate dehydrogenase-release assays, as well as cell death assays using flow cytometry, were performed to evaluate HepG2 cell proliferation following GM treatment. HepG2 cells were transfected with caspase-3 small interfering RNA and then treated with GM. Caspase-3 expression levels were determined by reverse transcription-quantitative PCR and western blotting. The present study showed that GM inhibited the growth of HepG2 cells and induced the proteolytic cleavage of caspase 3, with concomitant cleavage of gasdermin E (GSDME), by markedly increasing the production of reactive oxygen species (ROS). This led to caspase 3-dependent cleavage of GSDME, thereby promoting pyroptosis in HepG2 cells. However, these changes were rescued by ROS scavengers, such as N-acetylcysteine. Furthermore, GM inhibited tumor growth by promoting the cleavage of caspase 3 and GSDME in HepG2 cell xenograft models. These results indicated that GM induced GSDME-dependent pyroptosis through caspase 3 activation, at least in part, by damaging the mitochondria and enhancing ROS production, thereby supporting the possible development of GM as a candidate for the prevention and treatment of liver cancer.
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spelling pubmed-92045512022-06-22 Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis Sun, Xinfeng Zhong, Xin Ma, Wenfeng Feng, Wenxing Huang, Qi Ma, Mengqing Lv, Minling Hu, Rui Han, Zhiyi Li, Jing Zhou, Xiaozhou Exp Ther Med Articles Liver cancer is a highly lethal malignancy. Despite considerable efforts made in recent years, the prognosis of patients with liver cancer remains poor. Curcuma zedoaria (known as Ezhu in Chinese) is widely prescribed in traditional Chinese medicine. Germacrone (GM) is a sesquiterpene constituent derived from the essential oil of Ezhu, and exerts anti-carcinogenic effects by inducing apoptosis in various cancer cells. The present study investigated the potential mechanism of GM in HepG2 cells. Cell Counting Kit-8, colony-formation and lactate dehydrogenase-release assays, as well as cell death assays using flow cytometry, were performed to evaluate HepG2 cell proliferation following GM treatment. HepG2 cells were transfected with caspase-3 small interfering RNA and then treated with GM. Caspase-3 expression levels were determined by reverse transcription-quantitative PCR and western blotting. The present study showed that GM inhibited the growth of HepG2 cells and induced the proteolytic cleavage of caspase 3, with concomitant cleavage of gasdermin E (GSDME), by markedly increasing the production of reactive oxygen species (ROS). This led to caspase 3-dependent cleavage of GSDME, thereby promoting pyroptosis in HepG2 cells. However, these changes were rescued by ROS scavengers, such as N-acetylcysteine. Furthermore, GM inhibited tumor growth by promoting the cleavage of caspase 3 and GSDME in HepG2 cell xenograft models. These results indicated that GM induced GSDME-dependent pyroptosis through caspase 3 activation, at least in part, by damaging the mitochondria and enhancing ROS production, thereby supporting the possible development of GM as a candidate for the prevention and treatment of liver cancer. D.A. Spandidos 2022-05-20 /pmc/articles/PMC9204551/ /pubmed/35747157 http://dx.doi.org/10.3892/etm.2022.11383 Text en Copyright: © Sun et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Sun, Xinfeng
Zhong, Xin
Ma, Wenfeng
Feng, Wenxing
Huang, Qi
Ma, Mengqing
Lv, Minling
Hu, Rui
Han, Zhiyi
Li, Jing
Zhou, Xiaozhou
Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis
title Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis
title_full Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis
title_fullStr Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis
title_full_unstemmed Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis
title_short Germacrone induces caspase-3/GSDME activation and enhances ROS production, causing HepG2 pyroptosis
title_sort germacrone induces caspase-3/gsdme activation and enhances ros production, causing hepg2 pyroptosis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204551/
https://www.ncbi.nlm.nih.gov/pubmed/35747157
http://dx.doi.org/10.3892/etm.2022.11383
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