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Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine
Oxeiptosis is a recently identified reactive oxygen species (ROS)-sensitive, caspase independent, non-inflammatory regulated cell death pathway. The activation of Kelch-like ECH-associated protein 1-Phosphoglycerate mutase 5-Apoptosis inducing factor mitochondria associated 1 (KEAP1-PGAM5-AIFM1) pat...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011521/ https://www.ncbi.nlm.nih.gov/pubmed/36914635 http://dx.doi.org/10.1038/s41420-023-01376-3 |
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author | Pallichankandy, Siraj Thayyullathil, Faisal Cheratta, Anees Rahman Subburayan, Karthikeyan Alakkal, Ameer Sultana, Mehar Drou, Nizar Arshad, Muhammad Tariq, Saeed Galadari, Sehamuddin |
author_facet | Pallichankandy, Siraj Thayyullathil, Faisal Cheratta, Anees Rahman Subburayan, Karthikeyan Alakkal, Ameer Sultana, Mehar Drou, Nizar Arshad, Muhammad Tariq, Saeed Galadari, Sehamuddin |
author_sort | Pallichankandy, Siraj |
collection | PubMed |
description | Oxeiptosis is a recently identified reactive oxygen species (ROS)-sensitive, caspase independent, non-inflammatory regulated cell death pathway. The activation of Kelch-like ECH-associated protein 1-Phosphoglycerate mutase 5-Apoptosis inducing factor mitochondria associated 1 (KEAP1-PGAM5-AIFM1) pathway is the key signaling event in the execution of oxeiptosis. In the present study, we demonstrate that sanguinarine (SNG), a quaternary benzophenanthridine alkaloid, induces oxeiptosis in human colorectal cancer (CRC) cells via ROS, specifically hydrogen peroxide (H(2)O(2))-dependent activation of KEAP1-PGAM5-AIFM1 signaling axis. Whilst, knockdown of KEAP1, PGAM5, and AIFM1 largely abolishes SNG-induced oxeiptosis, hence reinforcing the importance of the role of this pathway in the SNG-mediated cytotoxicity. Moreover, extracellular addition of H(2)O(2) sensitizes SNG-induced oxeiptosis in CRC cells, while removal of intracellular ROS by ROS scavengers, not only alleviated the overproduction of ROS caused by SNG, but also reversed the biochemical events associated with oxeiptosis. Finally, in vivo study demonstrates that SNG effectively reduces the tumor growth in HT-29 xenograft mouse model through features associated with oxeiptosis. This study highlights oxeiptosis as a novel tumor suppressive mechanism and further investigation of the role of oxeiptosis in cancer treatment is warranted. |
format | Online Article Text |
id | pubmed-10011521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100115212023-03-15 Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine Pallichankandy, Siraj Thayyullathil, Faisal Cheratta, Anees Rahman Subburayan, Karthikeyan Alakkal, Ameer Sultana, Mehar Drou, Nizar Arshad, Muhammad Tariq, Saeed Galadari, Sehamuddin Cell Death Discov Article Oxeiptosis is a recently identified reactive oxygen species (ROS)-sensitive, caspase independent, non-inflammatory regulated cell death pathway. The activation of Kelch-like ECH-associated protein 1-Phosphoglycerate mutase 5-Apoptosis inducing factor mitochondria associated 1 (KEAP1-PGAM5-AIFM1) pathway is the key signaling event in the execution of oxeiptosis. In the present study, we demonstrate that sanguinarine (SNG), a quaternary benzophenanthridine alkaloid, induces oxeiptosis in human colorectal cancer (CRC) cells via ROS, specifically hydrogen peroxide (H(2)O(2))-dependent activation of KEAP1-PGAM5-AIFM1 signaling axis. Whilst, knockdown of KEAP1, PGAM5, and AIFM1 largely abolishes SNG-induced oxeiptosis, hence reinforcing the importance of the role of this pathway in the SNG-mediated cytotoxicity. Moreover, extracellular addition of H(2)O(2) sensitizes SNG-induced oxeiptosis in CRC cells, while removal of intracellular ROS by ROS scavengers, not only alleviated the overproduction of ROS caused by SNG, but also reversed the biochemical events associated with oxeiptosis. Finally, in vivo study demonstrates that SNG effectively reduces the tumor growth in HT-29 xenograft mouse model through features associated with oxeiptosis. This study highlights oxeiptosis as a novel tumor suppressive mechanism and further investigation of the role of oxeiptosis in cancer treatment is warranted. Nature Publishing Group UK 2023-03-13 /pmc/articles/PMC10011521/ /pubmed/36914635 http://dx.doi.org/10.1038/s41420-023-01376-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Pallichankandy, Siraj Thayyullathil, Faisal Cheratta, Anees Rahman Subburayan, Karthikeyan Alakkal, Ameer Sultana, Mehar Drou, Nizar Arshad, Muhammad Tariq, Saeed Galadari, Sehamuddin Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine |
title | Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine |
title_full | Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine |
title_fullStr | Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine |
title_full_unstemmed | Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine |
title_short | Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine |
title_sort | targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011521/ https://www.ncbi.nlm.nih.gov/pubmed/36914635 http://dx.doi.org/10.1038/s41420-023-01376-3 |
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