dc.contributor.author |
Okuda, Kazuhide S |
|
dc.contributor.author |
Ng, Mei Fong |
|
dc.contributor.author |
Ruslan, Nur Faizah |
|
dc.contributor.author |
Bower, Neil I |
|
dc.contributor.author |
Song, Dedrick Soon Seng |
|
dc.contributor.author |
Chen, Huijun |
|
dc.contributor.author |
Baek, Sungmin |
|
dc.contributor.author |
Crosier, Philip S |
|
dc.contributor.author |
Koltowska, Katarzyna |
|
dc.contributor.author |
Astin, Jonathan W |
|
dc.contributor.author |
Tan, Pei Jean |
|
dc.contributor.author |
Hogan, Benjamin M |
|
dc.contributor.author |
Patel, Vyomesh |
|
dc.coverage.spatial |
Switzerland |
|
dc.date.accessioned |
2023-12-05T20:57:20Z |
|
dc.date.available |
2023-12-05T20:57:20Z |
|
dc.date.issued |
2021-06 |
|
dc.identifier.citation |
(2021). Pharmaceuticals, 14(7), 614-. |
|
dc.identifier.issn |
1424-8247 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/66739 |
|
dc.description.abstract |
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. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
MDPI |
|
dc.relation.ispartofseries |
Pharmaceuticals (Basel, Switzerland) |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
3,4-Difluorobenzocurcumin |
|
dc.subject |
Erk |
|
dc.subject |
Vegfc |
|
dc.subject |
Vegfr3 |
|
dc.subject |
lymphatic |
|
dc.subject |
zebrafish |
|
dc.subject |
3214 Pharmacology and Pharmaceutical Sciences |
|
dc.subject |
32 Biomedical and Clinical Sciences |
|
dc.subject |
Cancer |
|
dc.subject |
5 Development of treatments and therapeutic interventions |
|
dc.subject |
5.1 Pharmaceuticals |
|
dc.subject |
2 Aetiology |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
Cardiovascular |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Chemistry, Medicinal |
|
dc.subject |
Pharmacology & Pharmacy |
|
dc.subject |
GROWTH-FACTOR-C |
|
dc.subject |
HYALURONAN RECEPTOR LYVE-1 |
|
dc.subject |
IN-VIVO |
|
dc.subject |
TUMOR LYMPHANGIOGENESIS |
|
dc.subject |
LYMPHATIC VASCULATURE |
|
dc.subject |
CORNEAL LYMPHANGIOGENESIS |
|
dc.subject |
CURCUMIN |
|
dc.subject |
ANGIOGENESIS |
|
dc.subject |
EXPRESSION |
|
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
|
dc.title |
3,4-Difluorobenzocurcumin Inhibits Vegfc-Vegfr3-Erk Signalling to Block Developmental Lymphangiogenesis in Zebrafish |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.3390/ph14070614 |
|
pubs.issue |
7 |
|
pubs.begin-page |
614 |
|
pubs.volume |
14 |
|
dc.date.updated |
2023-11-22T19:09:52Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
34206901 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/34206901 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
858684 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Molecular Medicine |
|
dc.identifier.eissn |
1424-8247 |
|
dc.identifier.pii |
ph14070614 |
|
pubs.number |
ARTN 614 |
|
pubs.record-created-at-source-date |
2023-11-23 |
|
pubs.online-publication-date |
2021-06-26 |
|