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The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation

Non-small cell lung cancer (NSCLC) is the leading cause of death in lung cancer due to its aggressiveness and rapid migration. The potent antitumor effect of Smp24, an antimicrobial peptide derived from Egyptian scorpion Scorpio maurus palmatus via damaging the membrane and cytoskeleton have been re...

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Autores principales: Guo, Ruiyin, Chen, Xuewen, Nguyen, Tienthanh, Chai, Jinwei, Gao, Yahua, Wu, Jiena, Li, Jinqiao, Abdel-Rahman, Mohamed A., Chen, Xin, Xu, Xueqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502404/
https://www.ncbi.nlm.nih.gov/pubmed/36136528
http://dx.doi.org/10.3390/toxins14090590
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author Guo, Ruiyin
Chen, Xuewen
Nguyen, Tienthanh
Chai, Jinwei
Gao, Yahua
Wu, Jiena
Li, Jinqiao
Abdel-Rahman, Mohamed A.
Chen, Xin
Xu, Xueqing
author_facet Guo, Ruiyin
Chen, Xuewen
Nguyen, Tienthanh
Chai, Jinwei
Gao, Yahua
Wu, Jiena
Li, Jinqiao
Abdel-Rahman, Mohamed A.
Chen, Xin
Xu, Xueqing
author_sort Guo, Ruiyin
collection PubMed
description Non-small cell lung cancer (NSCLC) is the leading cause of death in lung cancer due to its aggressiveness and rapid migration. The potent antitumor effect of Smp24, an antimicrobial peptide derived from Egyptian scorpion Scorpio maurus palmatus via damaging the membrane and cytoskeleton have been reported earlier. However, its effects on mitochondrial functions and ROS accumulation in human lung cancer cells remain unknown. In the current study, we discovered that Smp24 can interact with the cell membrane and be internalized into A549 cells via endocytosis, followed by targeting mitochondria and affect mitochondrial function, which significantly causes ROS overproduction, altering mitochondrial membrane potential and the expression of cell cycle distribution-related proteins, mitochondrial apoptotic pathway, MAPK, as well as PI3K/Akt/mTOR/FAK signaling pathways. In summary, the antitumor effect of Smp24 against A549 cells is related to the induction of apoptosis, autophagy plus cell cycle arrest via mitochondrial dysfunction, and ROS accumulation. Accordingly, our findings shed light on the anticancer mechanism of Smp24, which may contribute to its further development as a potential agent in the treatment of lung cancer cells.
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spelling pubmed-95024042022-09-24 The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation Guo, Ruiyin Chen, Xuewen Nguyen, Tienthanh Chai, Jinwei Gao, Yahua Wu, Jiena Li, Jinqiao Abdel-Rahman, Mohamed A. Chen, Xin Xu, Xueqing Toxins (Basel) Article Non-small cell lung cancer (NSCLC) is the leading cause of death in lung cancer due to its aggressiveness and rapid migration. The potent antitumor effect of Smp24, an antimicrobial peptide derived from Egyptian scorpion Scorpio maurus palmatus via damaging the membrane and cytoskeleton have been reported earlier. However, its effects on mitochondrial functions and ROS accumulation in human lung cancer cells remain unknown. In the current study, we discovered that Smp24 can interact with the cell membrane and be internalized into A549 cells via endocytosis, followed by targeting mitochondria and affect mitochondrial function, which significantly causes ROS overproduction, altering mitochondrial membrane potential and the expression of cell cycle distribution-related proteins, mitochondrial apoptotic pathway, MAPK, as well as PI3K/Akt/mTOR/FAK signaling pathways. In summary, the antitumor effect of Smp24 against A549 cells is related to the induction of apoptosis, autophagy plus cell cycle arrest via mitochondrial dysfunction, and ROS accumulation. Accordingly, our findings shed light on the anticancer mechanism of Smp24, which may contribute to its further development as a potential agent in the treatment of lung cancer cells. MDPI 2022-08-27 /pmc/articles/PMC9502404/ /pubmed/36136528 http://dx.doi.org/10.3390/toxins14090590 Text en © 2022 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
Guo, Ruiyin
Chen, Xuewen
Nguyen, Tienthanh
Chai, Jinwei
Gao, Yahua
Wu, Jiena
Li, Jinqiao
Abdel-Rahman, Mohamed A.
Chen, Xin
Xu, Xueqing
The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation
title The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation
title_full The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation
title_fullStr The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation
title_full_unstemmed The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation
title_short The Strong Anti-Tumor Effect of Smp24 in Lung Adenocarcinoma A549 Cells Depends on Its Induction of Mitochondrial Dysfunctions and ROS Accumulation
title_sort strong anti-tumor effect of smp24 in lung adenocarcinoma a549 cells depends on its induction of mitochondrial dysfunctions and ros accumulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502404/
https://www.ncbi.nlm.nih.gov/pubmed/36136528
http://dx.doi.org/10.3390/toxins14090590
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