G9a-targeted chaetocin induces pyroptosis of gastric cancer cells
Objective: To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms. Methods: The proliferation of gastric cancer cells was detected by trypan blue staining. Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and p...
Published in: | Asian Pacific Journal of Tropical Biomedicine |
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Wolters Kluwer Medknow Publications
2023
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Online Access: | https://doi.org/10.4103/2221-1691.378601 https://doaj.org/article/bccf590c054746089f29e5340658f41a |
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ftdoajarticles:oai:doaj.org/article:bccf590c054746089f29e5340658f41a 2024-09-09T19:27:30+00:00 G9a-targeted chaetocin induces pyroptosis of gastric cancer cells Mian-Qing Huang Gui-Lan Tao Li-Fang Han Shu-Hong Tian Peng Zhou 2023-01-01T00:00:00Z https://doi.org/10.4103/2221-1691.378601 https://doaj.org/article/bccf590c054746089f29e5340658f41a EN eng Wolters Kluwer Medknow Publications http://www.apjtb.org/article.asp?issn=2221-1691;year=2023;volume=13;issue=6;spage=268;epage=276;aulast=Huang https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.378601 https://doaj.org/article/bccf590c054746089f29e5340658f41a Asian Pacific Journal of Tropical Biomedicine, Vol 13, Iss 6, Pp 268-276 (2023) chaetocin gastric cancer pyroptosis g9a gsdme Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 article 2023 ftdoajarticles https://doi.org/10.4103/2221-1691.378601 2024-08-05T17:49:19Z Objective: To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms. Methods: The proliferation of gastric cancer cells was detected by trypan blue staining. Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis. Cellular ultrastructure was observed by transmission electron microscopy. The levels of p-mixed lineage kinase domain-like (MLKL), gasdermin-D (GSDMD), gasdermin E (GSDME), N-GSDMD, and N-GSDME proteins were detected by Western blotting. In addition, lactate dehydrogenase (LDH) release assay was used to verify pyroptosis induced by chaetocin, and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms. Results: Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS, HGC27, MKN28, and SGC7901 gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis. Significant ultrastructure changes, such as chromatin condensation, vacuolization, disrupted mitochondrial cristae, and increased nuclear occupancy, were observed after treatment with chaetocin in SGC7901 cells. Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells, LDH release, and the ratio of N-GSDME/ GSDME (P<0.01), which were reversed by Z-DEVD-FMK. In addition, chaetocin did not affect the expression of GSDMD. G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release (P>0.05). Conclusions: In addition to inducing apoptosis, chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway. G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Asian Pacific Journal of Tropical Biomedicine 13 6 268 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
chaetocin gastric cancer pyroptosis g9a gsdme Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
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chaetocin gastric cancer pyroptosis g9a gsdme Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 Mian-Qing Huang Gui-Lan Tao Li-Fang Han Shu-Hong Tian Peng Zhou G9a-targeted chaetocin induces pyroptosis of gastric cancer cells |
topic_facet |
chaetocin gastric cancer pyroptosis g9a gsdme Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
description |
Objective: To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms. Methods: The proliferation of gastric cancer cells was detected by trypan blue staining. Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis. Cellular ultrastructure was observed by transmission electron microscopy. The levels of p-mixed lineage kinase domain-like (MLKL), gasdermin-D (GSDMD), gasdermin E (GSDME), N-GSDMD, and N-GSDME proteins were detected by Western blotting. In addition, lactate dehydrogenase (LDH) release assay was used to verify pyroptosis induced by chaetocin, and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms. Results: Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS, HGC27, MKN28, and SGC7901 gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis. Significant ultrastructure changes, such as chromatin condensation, vacuolization, disrupted mitochondrial cristae, and increased nuclear occupancy, were observed after treatment with chaetocin in SGC7901 cells. Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells, LDH release, and the ratio of N-GSDME/ GSDME (P<0.01), which were reversed by Z-DEVD-FMK. In addition, chaetocin did not affect the expression of GSDMD. G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release (P>0.05). Conclusions: In addition to inducing apoptosis, chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway. G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells. |
format |
Article in Journal/Newspaper |
author |
Mian-Qing Huang Gui-Lan Tao Li-Fang Han Shu-Hong Tian Peng Zhou |
author_facet |
Mian-Qing Huang Gui-Lan Tao Li-Fang Han Shu-Hong Tian Peng Zhou |
author_sort |
Mian-Qing Huang |
title |
G9a-targeted chaetocin induces pyroptosis of gastric cancer cells |
title_short |
G9a-targeted chaetocin induces pyroptosis of gastric cancer cells |
title_full |
G9a-targeted chaetocin induces pyroptosis of gastric cancer cells |
title_fullStr |
G9a-targeted chaetocin induces pyroptosis of gastric cancer cells |
title_full_unstemmed |
G9a-targeted chaetocin induces pyroptosis of gastric cancer cells |
title_sort |
g9a-targeted chaetocin induces pyroptosis of gastric cancer cells |
publisher |
Wolters Kluwer Medknow Publications |
publishDate |
2023 |
url |
https://doi.org/10.4103/2221-1691.378601 https://doaj.org/article/bccf590c054746089f29e5340658f41a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Asian Pacific Journal of Tropical Biomedicine, Vol 13, Iss 6, Pp 268-276 (2023) |
op_relation |
http://www.apjtb.org/article.asp?issn=2221-1691;year=2023;volume=13;issue=6;spage=268;epage=276;aulast=Huang https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.378601 https://doaj.org/article/bccf590c054746089f29e5340658f41a |
op_doi |
https://doi.org/10.4103/2221-1691.378601 |
container_title |
Asian Pacific Journal of Tropical Biomedicine |
container_volume |
13 |
container_issue |
6 |
container_start_page |
268 |
_version_ |
1809896928191709184 |