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Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells
Artonin E is a prenylated flavonoid compound isolated from the stem bark of Artocarpus elasticus. This phytochemical has been previously reported to be drug-like with full compliance to Lipinski’s rule of five and good physicochemical properties when compared with 95% of orally available drugs. It h...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367776/ https://www.ncbi.nlm.nih.gov/pubmed/28356713 http://dx.doi.org/10.2147/DDDT.S124324 |
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author | Etti, Imaobong Christopher Rasedee, Abdullah Hashim, Najihah Mohd Abdul, Ahmad Bustamam Kadir, Arifah Yeap, Swee Keong Waziri, Peter Malami, Ibrahim Lim, Kian Lam Etti, Christopher J |
author_facet | Etti, Imaobong Christopher Rasedee, Abdullah Hashim, Najihah Mohd Abdul, Ahmad Bustamam Kadir, Arifah Yeap, Swee Keong Waziri, Peter Malami, Ibrahim Lim, Kian Lam Etti, Christopher J |
author_sort | Etti, Imaobong Christopher |
collection | PubMed |
description | Artonin E is a prenylated flavonoid compound isolated from the stem bark of Artocarpus elasticus. This phytochemical has been previously reported to be drug-like with full compliance to Lipinski’s rule of five and good physicochemical properties when compared with 95% of orally available drugs. It has also been shown to possess unique medicinal properties that can be utilized in view of alleviating most human disease conditions. In this study, we investigated the cytotoxic mechanism of Artonin E in MCF-7 breast cancer cells, which has so far not been reported. In this context, Artonin E significantly suppressed the breast cancer cell’s viability while inducing apoptosis in a dose-dependent manner. This apoptosis induction was caspase dependent, and it is mediated mainly through the intrinsic pathway with the elevation of total reactive oxygen species. Gene and protein expression studies revealed significant upregulation of cytochrome c, Bax, caspases 7 and 9, and p21 in Artonin E-treated MCF-7 cells, while MAPK and cyclin D were downregulated. Livin, a member of the inhibitors of apoptosis, whose upregulation has been noted to precede chemotherapeutic resistance and apoptosis evasion was remarkably repressed. In all, Artonin E stood high as a potential agent in the treatment of breast cancer. |
format | Online Article Text |
id | pubmed-5367776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53677762017-03-29 Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells Etti, Imaobong Christopher Rasedee, Abdullah Hashim, Najihah Mohd Abdul, Ahmad Bustamam Kadir, Arifah Yeap, Swee Keong Waziri, Peter Malami, Ibrahim Lim, Kian Lam Etti, Christopher J Drug Des Devel Ther Original Research Artonin E is a prenylated flavonoid compound isolated from the stem bark of Artocarpus elasticus. This phytochemical has been previously reported to be drug-like with full compliance to Lipinski’s rule of five and good physicochemical properties when compared with 95% of orally available drugs. It has also been shown to possess unique medicinal properties that can be utilized in view of alleviating most human disease conditions. In this study, we investigated the cytotoxic mechanism of Artonin E in MCF-7 breast cancer cells, which has so far not been reported. In this context, Artonin E significantly suppressed the breast cancer cell’s viability while inducing apoptosis in a dose-dependent manner. This apoptosis induction was caspase dependent, and it is mediated mainly through the intrinsic pathway with the elevation of total reactive oxygen species. Gene and protein expression studies revealed significant upregulation of cytochrome c, Bax, caspases 7 and 9, and p21 in Artonin E-treated MCF-7 cells, while MAPK and cyclin D were downregulated. Livin, a member of the inhibitors of apoptosis, whose upregulation has been noted to precede chemotherapeutic resistance and apoptosis evasion was remarkably repressed. In all, Artonin E stood high as a potential agent in the treatment of breast cancer. Dove Medical Press 2017-03-20 /pmc/articles/PMC5367776/ /pubmed/28356713 http://dx.doi.org/10.2147/DDDT.S124324 Text en © 2017 Etti et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Etti, Imaobong Christopher Rasedee, Abdullah Hashim, Najihah Mohd Abdul, Ahmad Bustamam Kadir, Arifah Yeap, Swee Keong Waziri, Peter Malami, Ibrahim Lim, Kian Lam Etti, Christopher J Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells |
title | Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells |
title_full | Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells |
title_fullStr | Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells |
title_full_unstemmed | Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells |
title_short | Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells |
title_sort | artonin e induces p53-independent g1 cell cycle arrest and apoptosis through ros-mediated mitochondrial pathway and livin suppression in mcf-7 cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367776/ https://www.ncbi.nlm.nih.gov/pubmed/28356713 http://dx.doi.org/10.2147/DDDT.S124324 |
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