Original Articles: Basic ScienceAnti-angiogenic effects of mangiferin and mechanism of action in metastatic melanomaDelgado-Hernández, Renéa; Hernández-Balmaseda, Ivonesb; Rodeiro-Guerra, Idaniab; Cesar Rodriguez Gonzalez, Julioc; De Wever, Olivierd; Logie, Emiliee; Declerck, Kene; Pérez-Novo, Claudinae; Vanden Berghe, WimeAuthor Information aCentro de Estudios para las Investigaciones y Evaluaciones Biológicas (CEIEB), Instituto de Farmacia y Alimentos (IFAL), Universidad de La Habana (UH) bLaboratorio de Farmacología, Instituto de Ciencias del Mar (ICIMAR), CITMA cCentro de Investigación y Desarrollo de Medicamentos (CIDEM), La Habana, Cuba dLaboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, UZ-Gent, Gent eLaboratory of Proteinchemistry, Proteomics & Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium Received 14 September 2018 Accepted 5 September 2019 Correspondence to Wim Vanden Berghe, PhD, Laboratory of Proteinchemistry, Proteomics & Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, S4.25, Universiteitsplein 1, 2610 Antwerp, Belgium, Tel: +32 3 265 26 57; fax +32 3 265 23 39; e-mail: [email protected] Melanoma Research: February 2020 - Volume 30 - Issue 1 - p 39-51 doi: 10.1097/CMR.0000000000000647 Buy Metrics Abstract Advanced metastatic melanoma, one of the most aggressive skin malignancies, is currently without reliable therapy. The process of angiogenesis is crucial for progression and metastasis of the majority of solid tumors including melanomas. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone which exerts many pharmacological activities against cancer-inflammation. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we demonstrate that mangiferin interferes with inflammation, lipid and calcium signaling which selectively inhibits multiple NFkB target genes including interleukin-6, tumor necrosis factor, interferon gamma, vascular endothelial growth factor receptor 2, plasminogen activator urokinase, matrix metalloprotease 19, C-C Motif Chemokine Ligand 2 and placental growth factor. This abrogates angiogenic and invasive processes and capillary tube formation of metastatic melanoma cells as well as human placental blood vessel explants in-vitro and blocks angiogenesis characteristic of the chicken egg chorioallantoic membrane assay and in melanoma syngeneic studies in vivo. The results obtained in this research illustrate promising anti-angiogenic effects of the natural glucosylxanthone mangiferin for further (pre)clinical studies in melanoma cancer patients. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.