Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells

Abstract The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol has shown anti-proliferative effects against the human non-small cell lung cancer A549 cell line. M22 showed significant anti-proliferative activity at 6.80 μM and increased accumulation of G1 cells and effectiv...

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Autores principales: Yao Yuan, Jiewei Wu, Bailin Li, Jia Niu, Haibo Tan, Shengxiang Qiu
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/daa7bdd317e7443f8394c982dfbde5ec
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spelling oai:doaj.org-article:daa7bdd317e7443f8394c982dfbde5ec2021-12-02T15:08:24ZRegulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells10.1038/s41598-018-19368-02045-2322https://doaj.org/article/daa7bdd317e7443f8394c982dfbde5ec2018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19368-0https://doaj.org/toc/2045-2322Abstract The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol has shown anti-proliferative effects against the human non-small cell lung cancer A549 cell line. M22 showed significant anti-proliferative activity at 6.80 μM and increased accumulation of G1 cells and effectively suppressed expression of the G1 arrest-related genes cyclins D1 and E1, CDK2 and CDC25A. This was further confirmed by Western blotting demonstrating decreased cyclin D1 and CDC25A protein levels. Furthermore, M22 caused induction of apoptosis that downregulated the anti-apoptotic BCL-2 gene and increased expression of BAX, CASP3 and CASP9 as well as the APAF1 gene. The effect of caspase-induced apoptosis was confirmed by an increase in reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP). Taken together, our findings indicated that M22 possessed potent anti-proliferative and apoptotic activities.Yao YuanJiewei WuBailin LiJia NiuHaibo TanShengxiang QiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yao Yuan
Jiewei Wu
Bailin Li
Jia Niu
Haibo Tan
Shengxiang Qiu
Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells
description Abstract The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol has shown anti-proliferative effects against the human non-small cell lung cancer A549 cell line. M22 showed significant anti-proliferative activity at 6.80 μM and increased accumulation of G1 cells and effectively suppressed expression of the G1 arrest-related genes cyclins D1 and E1, CDK2 and CDC25A. This was further confirmed by Western blotting demonstrating decreased cyclin D1 and CDC25A protein levels. Furthermore, M22 caused induction of apoptosis that downregulated the anti-apoptotic BCL-2 gene and increased expression of BAX, CASP3 and CASP9 as well as the APAF1 gene. The effect of caspase-induced apoptosis was confirmed by an increase in reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP). Taken together, our findings indicated that M22 possessed potent anti-proliferative and apoptotic activities.
format article
author Yao Yuan
Jiewei Wu
Bailin Li
Jia Niu
Haibo Tan
Shengxiang Qiu
author_facet Yao Yuan
Jiewei Wu
Bailin Li
Jia Niu
Haibo Tan
Shengxiang Qiu
author_sort Yao Yuan
title Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells
title_short Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells
title_full Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells
title_fullStr Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells
title_full_unstemmed Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis-inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells
title_sort regulation of signaling pathways involved in the anti-proliferative and apoptosis-inducing effects of m22 against non-small cell lung adenocarcinoma a549 cells
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/daa7bdd317e7443f8394c982dfbde5ec
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