Exploring the Antiangiogenic Potential of Solomonamide A Bioactive Precursors: In Vitro and In Vivo Evidences of the Inhibitory Activity of Solo F-OH During Angiogenesis
Paloma Carrillo,
Beatriz Martínez-Poveda,
Iván Cheng-Sánchez,
Jessica Guerra,
Chiara Tobia,
J. Manuel López-Romero,
Francisco Sarabia,
Miguel Ángel Medina,
Ana R. Quesada
Affiliations
Paloma Carrillo
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Andalucía Tech, 29071 Málaga, Spain
Beatriz Martínez-Poveda
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Andalucía Tech, 29071 Málaga, Spain
Iván Cheng-Sánchez
Department of Organic Chemistry, Faculty of Sciences, University of Málaga, Andalucía Tech, 29071 Málaga, Spain
Jessica Guerra
Department of Molecular and Translational Medicine, Experimental Oncology and Immunology, School of Medicine, University of Brescia, 25125 Brescia, Italy
Chiara Tobia
Department of Molecular and Translational Medicine, Experimental Oncology and Immunology, School of Medicine, University of Brescia, 25125 Brescia, Italy
J. Manuel López-Romero
Department of Organic Chemistry, Faculty of Sciences, University of Málaga, Andalucía Tech, 29071 Málaga, Spain
Francisco Sarabia
Department of Organic Chemistry, Faculty of Sciences, University of Málaga, Andalucía Tech, 29071 Málaga, Spain
Miguel Ángel Medina
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Andalucía Tech, 29071 Málaga, Spain
Ana R. Quesada
Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, Andalucía Tech, 29071 Málaga, Spain
Marine sponges are a prolific source of bioactive compounds. In this work, the putative antiangiogenic potential of a series of synthetic precursors of Solomonamide A, a cyclic peptide isolated from a marine sponge, was evaluated. By means of an in vitro screening, based on the inhibitory activity of endothelial tube formation, the compound Solo F–OH was selected for a deeper characterization of its antiangiogenic potential. Our results indicate that Solo F–OH is able to inhibit some key steps of the angiogenic process, including the proliferation, migration, and invasion of endothelial cells, as well as diminish their capability to degrade the extracellular matrix proteins. The antiangiogenic potential of Solo F–OH was confirmed by means of two different in vivo models: the chorioallantoic membrane (CAM) and the zebrafish yolk membrane (ZFYM) assays. The reduction in ERK1/2 and Akt phosphorylation in endothelial cells treated with Solo F–OH denotes that this compound could target the upstream components that are common to both pathways. Taken together, our results show a new and interesting biological activity of Solo F–OH as an inhibitor of the persistent and deregulated angiogenesis that characterizes cancer and other pathologies.
