Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner

Context Gambogic amide (GA-amide) is a non-peptide molecule that has high affinity for tropomyosin receptor kinase A (TrkA) and possesses robust neurotrophic activity, but its effect on angiogenesis is unclear. Objective The study investigates the antiangiogenic effect of GA-amide on endothelial cel...

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Autores principales:	Tongtong Sui, Bojun Qiu, Jiaorong Qu, Yuxin Wang, Kunnian Ran, Wei Han, Xiaozhong Peng
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	antiangiogenic akt/mtor plcγ/erk1/2 anticancer phytochemicals Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/71e716cae65a4e7eb8c52117ebb95918
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spelling	oai:doaj.org-article:71e716cae65a4e7eb8c52117ebb959182021-11-17T14:21:56ZGambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner1388-02091744-511610.1080/13880209.2021.1998140https://doaj.org/article/71e716cae65a4e7eb8c52117ebb959182021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1998140https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context Gambogic amide (GA-amide) is a non-peptide molecule that has high affinity for tropomyosin receptor kinase A (TrkA) and possesses robust neurotrophic activity, but its effect on angiogenesis is unclear. Objective The study investigates the antiangiogenic effect of GA-amide on endothelial cells (ECs). Materials and methods The viability of endothelial cells (ECs) treated with 0.1, 0.15, 0.2, 0.3, 0.4, and 0.5 μM GA-amide for 48 h was detected by MTS assay. Wound healing and angiogenesis assays were performed on cells treated with 0.2 μM GA-amide. Chicken eggs at day 7 post-fertilization were divided into the dimethyl sulfoxide (DMSO), bevacizumab (40 μg), and GA-amide (18.8 and 62.8 ng) groups to assess the antiangiogenic effect for 3 days. mRNA and protein expression in cells treated with 0.1, 0.2, 0.4, 0.8, and 1.2 μM GA-amide for 6 h was detected by qRT-PCR and Western blots, respectively. Results GA-amide inhibited HUVEC (IC50 = 0.1269 μM) and NhEC (IC50 = 0.1740 μM) proliferation, induced cell apoptosis, and inhibited the migration and angiogenesis at a relatively safe dose (0.2 μM) in vitro. GA-amide reduced the number of capillaries from 56 ± 14.67 (DMSO) to 20.3 ± 5.12 (62.8 ng) in chick chorioallantoic membrane (CAM) assay. However, inactivation of TrkA couldn’t reverse the antiangiogenic effect of GA-amide. Moreover, GA-amide suppressed the expression of VEGF and VEGFR2, and decreased activation of the AKT/mTOR and PLCγ/Erk1/2 pathways. Conclusions Considering the antiangiogenic effect of GA-amide, it might be developed as a useful agent for use in clinical combination therapies.Tongtong SuiBojun QiuJiaorong QuYuxin WangKunnian RanWei HanXiaozhong PengTaylor & Francis Grouparticleantiangiogenicakt/mtorplcγ/erk1/2anticancerphytochemicalsTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1566-1575 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antiangiogenic akt/mtor plcγ/erk1/2 anticancer phytochemicals Therapeutics. Pharmacology RM1-950
spellingShingle	antiangiogenic akt/mtor plcγ/erk1/2 anticancer phytochemicals Therapeutics. Pharmacology RM1-950 Tongtong Sui Bojun Qiu Jiaorong Qu Yuxin Wang Kunnian Ran Wei Han Xiaozhong Peng Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner
description	Context Gambogic amide (GA-amide) is a non-peptide molecule that has high affinity for tropomyosin receptor kinase A (TrkA) and possesses robust neurotrophic activity, but its effect on angiogenesis is unclear. Objective The study investigates the antiangiogenic effect of GA-amide on endothelial cells (ECs). Materials and methods The viability of endothelial cells (ECs) treated with 0.1, 0.15, 0.2, 0.3, 0.4, and 0.5 μM GA-amide for 48 h was detected by MTS assay. Wound healing and angiogenesis assays were performed on cells treated with 0.2 μM GA-amide. Chicken eggs at day 7 post-fertilization were divided into the dimethyl sulfoxide (DMSO), bevacizumab (40 μg), and GA-amide (18.8 and 62.8 ng) groups to assess the antiangiogenic effect for 3 days. mRNA and protein expression in cells treated with 0.1, 0.2, 0.4, 0.8, and 1.2 μM GA-amide for 6 h was detected by qRT-PCR and Western blots, respectively. Results GA-amide inhibited HUVEC (IC50 = 0.1269 μM) and NhEC (IC50 = 0.1740 μM) proliferation, induced cell apoptosis, and inhibited the migration and angiogenesis at a relatively safe dose (0.2 μM) in vitro. GA-amide reduced the number of capillaries from 56 ± 14.67 (DMSO) to 20.3 ± 5.12 (62.8 ng) in chick chorioallantoic membrane (CAM) assay. However, inactivation of TrkA couldn’t reverse the antiangiogenic effect of GA-amide. Moreover, GA-amide suppressed the expression of VEGF and VEGFR2, and decreased activation of the AKT/mTOR and PLCγ/Erk1/2 pathways. Conclusions Considering the antiangiogenic effect of GA-amide, it might be developed as a useful agent for use in clinical combination therapies.
format	article
author	Tongtong Sui Bojun Qiu Jiaorong Qu Yuxin Wang Kunnian Ran Wei Han Xiaozhong Peng
author_facet	Tongtong Sui Bojun Qiu Jiaorong Qu Yuxin Wang Kunnian Ran Wei Han Xiaozhong Peng
author_sort	Tongtong Sui
title	Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner
title_short	Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner
title_full	Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner
title_fullStr	Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner
title_full_unstemmed	Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner
title_sort	gambogic amide inhibits angiogenesis by suppressing vegf/vegfr2 in endothelial cells in a trka-independent manner
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/71e716cae65a4e7eb8c52117ebb95918
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Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner

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