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Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway

CONTEXT: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy. OBJECTIVE: To determine the antimetastatic effect and underlying...

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Autores principales: Qi, Xiaoyi, Chen, Yonglan, Liu, Sha, Liu, Li, Yu, Zehui, Yin, Ling, Fu, Lu, Deng, Mingming, Liang, Sicheng, Lü, Muhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128503/
https://www.ncbi.nlm.nih.gov/pubmed/37092313
http://dx.doi.org/10.1080/13880209.2023.2200787
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author Qi, Xiaoyi
Chen, Yonglan
Liu, Sha
Liu, Li
Yu, Zehui
Yin, Ling
Fu, Lu
Deng, Mingming
Liang, Sicheng
Lü, Muhan
author_facet Qi, Xiaoyi
Chen, Yonglan
Liu, Sha
Liu, Li
Yu, Zehui
Yin, Ling
Fu, Lu
Deng, Mingming
Liang, Sicheng
Lü, Muhan
author_sort Qi, Xiaoyi
collection PubMed
description CONTEXT: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy. OBJECTIVE: To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma. MATERIALS AND METHODS: CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. In vitro migration/invasion/western blot assay with 1, 1.5, 2 μM SAG and in vivo effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice. RESULTS: The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were −6.33, −6.31, and −6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells (p < 0.05) with IC(50) values of 2.378 μM and 2.719 μM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth. CONCLUSIONS: Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.
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spelling pubmed-101285032023-04-26 Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway Qi, Xiaoyi Chen, Yonglan Liu, Sha Liu, Li Yu, Zehui Yin, Ling Fu, Lu Deng, Mingming Liang, Sicheng Lü, Muhan Pharm Biol Research Article CONTEXT: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy. OBJECTIVE: To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma. MATERIALS AND METHODS: CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. In vitro migration/invasion/western blot assay with 1, 1.5, 2 μM SAG and in vivo effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice. RESULTS: The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were −6.33, −6.31, and −6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells (p < 0.05) with IC(50) values of 2.378 μM and 2.719 μM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth. CONCLUSIONS: Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic. Taylor & Francis 2023-04-24 /pmc/articles/PMC10128503/ /pubmed/37092313 http://dx.doi.org/10.1080/13880209.2023.2200787 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Article
Qi, Xiaoyi
Chen, Yonglan
Liu, Sha
Liu, Li
Yu, Zehui
Yin, Ling
Fu, Lu
Deng, Mingming
Liang, Sicheng
Lü, Muhan
Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
title Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
title_full Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
title_fullStr Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
title_full_unstemmed Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
title_short Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
title_sort sanguinarine inhibits melanoma invasion and migration by targeting the fak/pi3k/akt/mtor signalling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128503/
https://www.ncbi.nlm.nih.gov/pubmed/37092313
http://dx.doi.org/10.1080/13880209.2023.2200787
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