3,4-Difluorobenzocurcumin Inhibits Vegfc-Vegfr3-Erk Signalling to Block Developmental Lymphangiogenesis in Zebrafish
| العنوان: | 3,4-Difluorobenzocurcumin Inhibits Vegfc-Vegfr3-Erk Signalling to Block Developmental Lymphangiogenesis in Zebrafish |
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| المؤلفون: | Benjamin M. Hogan, Vyomesh Patel, Philip S. Crosier, Kazuhide S. Okuda, Jonathan W. Astin, Huijun Chen, Katarzyna Koltowska, Dedrick Soon Seng Song, Nur Faizah Ruslan, Neil I. Bower, Sungmin Baek, Pei Jean Tan, Mei Fong Ng |
| المصدر: | Pharmaceuticals Volume 14 Issue 7 Pharmaceuticals, Vol 14, Iss 614, p 614 (2021) |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Cell- och molekylärbiologi, 4-Difluorobenzocurcumin, Pharmaceutical Science, Biology, Article, lymphatic, Pharmacy and materia medica, In vivo, Vegfc, Drug Discovery, Kinase activity, Zebrafish, biology.organism_classification, zebrafish, Lymphangiogenesis, Vegfr3, RS1-441, Endothelial stem cell, Erk, Lymphatic system, Vascular endothelial growth factor C, Cancer research, Medicine, Molecular Medicine, Cell and Molecular Biology, 3,4-Difluorobenzocurcumin |
| الوصف: | Lymphangiogenesis, the formation of new lymphatic vessels from pre-existing vasculature, plays critical roles in disease, including in cancer metastasis and chronic inflammation. Preclinical and recent clinical studies have now demonstrated therapeutic utility for several anti-lymphangiogenic agents, but optimal agents and efficacy in different settings remain to be determined. We tested the anti-lymphangiogenic property of 3,4-Difluorobenzocurcumin (CDF), which has previously been implicated as an anti-cancer agent, using zebrafish embryos and cultured vascular endothelial cells. We used transgenic zebrafish labelling the lymphatic system and found that CDF potently inhibits lymphangiogenesis during embryonic development. We also found that the parent compound, Curcumin, does not inhibit lymphangiogenesis. CDF blocked lymphatic and venous sprouting, and lymphatic migration in the head and trunk of the embryo. Mechanistically, CDF impaired VEGFC-VEGFR3-ERK signalling in vitro and in vivo. In an in vivo pathological model of Vegfc-overexpression, treatment with CDF rescued endothelial cell hyperplasia. CDF did not inhibit the kinase activity of VEGFR3 yet displayed more prolonged activity in vivo than previously reported kinase inhibitors. These findings warrant further assessment of CDF and its mode of action as a candidate for use in metastasis and diseases of aberrant lymphangiogenesis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1424-8247 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a74ebdd0600c04ffef0bb07ef7e0372f http://europepmc.org/articles/PMC8308560 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a74ebdd0600c04ffef0bb07ef7e0372f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14248247 |
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