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Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS

Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found...

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Detalles Bibliográficos
Autores principales: Yang, Dong-Lin, Li, Yong, Ma, Shui-Qing, Zhang, Ya-Jun, Huang, Jiu-Hong, He, Liu-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095895/
https://www.ncbi.nlm.nih.gov/pubmed/37049976
http://dx.doi.org/10.3390/molecules28073211
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author Yang, Dong-Lin
Li, Yong
Ma, Shui-Qing
Zhang, Ya-Jun
Huang, Jiu-Hong
He, Liu-Jun
author_facet Yang, Dong-Lin
Li, Yong
Ma, Shui-Qing
Zhang, Ya-Jun
Huang, Jiu-Hong
He, Liu-Jun
author_sort Yang, Dong-Lin
collection PubMed
description Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC.
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spelling pubmed-100958952023-04-13 Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS Yang, Dong-Lin Li, Yong Ma, Shui-Qing Zhang, Ya-Jun Huang, Jiu-Hong He, Liu-Jun Molecules Article Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC. MDPI 2023-04-04 /pmc/articles/PMC10095895/ /pubmed/37049976 http://dx.doi.org/10.3390/molecules28073211 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Dong-Lin
Li, Yong
Ma, Shui-Qing
Zhang, Ya-Jun
Huang, Jiu-Hong
He, Liu-Jun
Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS
title Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS
title_full Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS
title_fullStr Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS
title_full_unstemmed Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS
title_short Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS
title_sort compound 275# induces mitochondria-mediated apoptosis and autophagy initiation in colorectal cancer cells through an accumulation of intracellular ros
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095895/
https://www.ncbi.nlm.nih.gov/pubmed/37049976
http://dx.doi.org/10.3390/molecules28073211
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