{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:11:14Z","timestamp":1778692274037,"version":"3.51.4"},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2\u2010methyl\u2010hydroquinone isolated from the culture broth of the marine fungus <jats:italic>Penicillium<\/jats:italic> sp. HL\u201085\u2010ALS5\u2010R004, to inhibit lymphangiogenesis <jats:italic>in vitro<\/jats:italic>, <jats:italic>ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D <jats:italic>in vitro<\/jats:italic> cultures and in the <jats:italic>ex vivo<\/jats:italic> mouse lymphatic ring assay. For <jats:italic>in vivo<\/jats:italic> approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Toluquinol inhibited LEC proliferation, migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment <jats:italic>in vitro<\/jats:italic>, blocked the development of the thoracic duct in zebrafish and reduced the VEGF\u2010C\u2010induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF\u2010C\u2010induced VEGFR\u20103 phosphorylation in a dose\u2010dependent manner and suppresses the phosphorylation of Akt and ERK1\/2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis\u2010related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13488","type":"journal-article","created":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T13:26:47Z","timestamp":1459171607000},"page":"1966-1987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF\u2010C\/VEGFR\u20103 signalling pathway"],"prefix":"10.1111","volume":"173","author":[{"given":"M","family":"Garc\u00eda\u2010Caballero","sequence":"first","affiliation":[{"name":"Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de G\u00e9noprot\u00e9omique Appliqu\u00e9\u2010Cancer (GIGA\u2010Cancer) University of Li\u00e8ge  Li\u00e8ge 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