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Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation
Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-do...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198376/ https://www.ncbi.nlm.nih.gov/pubmed/34071298 http://dx.doi.org/10.3390/molecules26113243 |
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author | Sun, Ai-Ling Mu, Wen-Wen Li, Yan-Mo Sun, Ya-Lei Li, Peng-Xiao Liu, Ren-Min Yang, Jie Liu, Guo-Yun |
author_facet | Sun, Ai-Ling Mu, Wen-Wen Li, Yan-Mo Sun, Ya-Lei Li, Peng-Xiao Liu, Ren-Min Yang, Jie Liu, Guo-Yun |
author_sort | Sun, Ai-Ling |
collection | PubMed |
description | Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2–C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2–C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation. |
format | Online Article Text |
id | pubmed-8198376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81983762021-06-14 Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation Sun, Ai-Ling Mu, Wen-Wen Li, Yan-Mo Sun, Ya-Lei Li, Peng-Xiao Liu, Ren-Min Yang, Jie Liu, Guo-Yun Molecules Article Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2–C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2–C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation. MDPI 2021-05-28 /pmc/articles/PMC8198376/ /pubmed/34071298 http://dx.doi.org/10.3390/molecules26113243 Text en © 2021 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 Sun, Ai-Ling Mu, Wen-Wen Li, Yan-Mo Sun, Ya-Lei Li, Peng-Xiao Liu, Ren-Min Yang, Jie Liu, Guo-Yun Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation |
title | Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation |
title_full | Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation |
title_fullStr | Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation |
title_full_unstemmed | Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation |
title_short | Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation |
title_sort | piperlongumine analogs promote a549 cell apoptosis through enhancing ros generation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198376/ https://www.ncbi.nlm.nih.gov/pubmed/34071298 http://dx.doi.org/10.3390/molecules26113243 |
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