دورية أكاديمية
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: | Kazuhide S. Okuda, Mei Fong Ng, Nur Faizah Ruslan, Neil I. Bower, Dedrick Soon Seng Song, Huijun Chen, Sungmin Baek, Philip S. Crosier, Katarzyna Koltowska, Jonathan W. Astin, Pei Jean Tan, Benjamin M. Hogan, Vyomesh Patel |
| المصدر: | Pharmaceuticals, Vol 14, Iss 7, p 614 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Pharmacy and materia medica |
| مصطلحات موضوعية: | 3,4-Difluorobenzocurcumin, zebrafish, lymphatic, Vegfc, Vegfr3, Erk, Medicine, Pharmacy and materia medica, RS1-441 |
| 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1424-8247 |
| Relation: | https://www.mdpi.com/1424-8247/14/7/614; https://doaj.org/toc/1424-8247 |
| DOI: | 10.3390/ph14070614 |
| URL الوصول: | https://doaj.org/article/9cccbc0b9d394f71a04ef23b0bbdf222 |
| رقم الأكسشن: | edsdoj.9cccbc0b9d394f71a04ef23b0bbdf222 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14248247 |
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| DOI: | 10.3390/ph14070614 |