NDLI: The Marine Fungal Metabolite, AD0157, Inhibits Angiogenesis by Targeting the Akt Signaling Pathway

Content Provider	PubMed Central
Author	García-caballero, Melissa Cañedo, Librada Antonio, Fernández-medarde Medina, Miguel Ángel Quesada, Ana R.
Copyright Year	2014
Abstract	In the course of a screening program for the inhibitors of angiogenesis from marine sources, AD0157, a pyrrolidinedione fungal metabolite, was selected for its angiosupressive properties. AD0157 inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results show that subtoxic doses of this compound inhibit certain functions of endothelial cells, namely, differentiation, migration and proteolytic capability. Inhibition of the mentioned essential steps of in vitro angiogenesis is in agreement with the observed antiangiogenic activity, substantiated by using two in vivo angiogenesis models, the chorioallantoic membrane and the zebrafish embryo neovascularization assays, and by the ex vivo mouse aortic ring assay. Our data indicate that AD0157 induces apoptosis in endothelial cells through chromatin condensation, DNA fragmentation, increases in the subG1 peak and caspase activation. The data shown here altogether indicate for the first time that AD0157 displays antiangiogenic effects, both in vitro and in vivo, that are exerted partly by targeting the Akt signaling pathway in activated endothelial cells. The fact that these effects are carried out at lower concentrations than those required for other inhibitors of angiogenesis makes AD0157 a new promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies.
Related Links	http://dx.doi.org/10.3390/md12010279
Ending Page	299
Page Count	21
Starting Page	279
File Format	PDF
ISSN	16603397
e-ISSN	16603397
Journal	Marine Drugs
Issue Number	1
Volume Number	12
Language	English
Publisher	MDPI
Publisher Date	2014-01-01
Access Restriction	Open
Rights Holder	MDPI
Subject Keyword	Drug Discovery Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmaceutical Science

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