Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway
AbstractContext 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 under...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2023.2200787 |
| _version_ | 1797234867267698688 |
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| author | Xiaoyi Qi Yonglan Chen Sha Liu Li Liu Zehui Yu Ling Yin Lu Fu Mingming Deng Sicheng Liang Muhan Lü |
| author_facet | Xiaoyi Qi Yonglan Chen Sha Liu Li Liu Zehui Yu Ling Yin Lu Fu Mingming Deng Sicheng Liang Muhan Lü |
| author_sort | Xiaoyi Qi |
| collection | DOAJ |
| description | AbstractContext 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 IC50 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. |
| first_indexed | 2024-03-09T00:09:41Z |
| format | Article |
| id | doaj.art-dadea27cc5844f979b2260be86b323d2 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-04-24T16:38:53Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-dadea27cc5844f979b2260be86b323d22024-03-29T11:10:26ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162023-12-0161169670910.1080/13880209.2023.2200787Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathwayXiaoyi Qi0Yonglan Chen1Sha Liu2Li Liu3Zehui Yu4Ling Yin5Lu Fu6Mingming Deng7Sicheng Liang8Muhan Lü9Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaThe Public Platform of Advanced Detecting Instruments, Public Center of Experimental Technology, Southwest Medical University, Luzhou, ChinaThe Public Platform of Advanced Detecting Instruments, Public Center of Experimental Technology, Southwest Medical University, Luzhou, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaAbstractContext 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 IC50 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.https://www.tandfonline.com/doi/10.1080/13880209.2023.2200787Network pharmacologymolecular dockingmetastasisadhesion |
| spellingShingle | Xiaoyi Qi Yonglan Chen Sha Liu Li Liu Zehui Yu Ling Yin Lu Fu Mingming Deng Sicheng Liang Muhan Lü Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway Pharmaceutical Biology Network pharmacology molecular docking metastasis adhesion |
| 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 | Network pharmacology molecular docking metastasis adhesion |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2023.2200787 |
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