RT Conference Proceedings
T1 AD0157, a pyrrolidinedione fungal metabolite, inhibits angiogenesis by targeting the Akt signaling pathway
A1 García-Caballero, Melissa
A1 Cañedo, Librada
A1 Fernández-Medarde, Antonio
A1 Rodríguez-Quesada, Ana María
A1 Medina-Torres, Miguel Ángel
K1 Neovascularización
AB In the course of a screening program for the inhibitors of angiogenesis from marinesources, AD0157, a pyrrolidinedione fungal metabolite, was selected for itsangiosupressive properties. AD0157 inhibited the growth of endothelial and tumor cells inculture in the micromolar range. Our results show that subtoxic doses of this compoundinhibit certain functions of endothelial cells, namely, differentiation, migration andproteolytic capability. Inhibition of the mentioned essential steps of in vitro angiogenesis isin agreement with the observed antiangiogenic activity, substantiated by using two in vivoangiogenesis models, the chorioallantoic membrane and the zebrafish embryoneovascularization assays, and by the ex vivo mouse aortic ring assay. Our data indicatethat AD0157 induces apoptosis in endothelial cells through chromatin condensation, DNAfragmentation, increases in the subG1 peak and caspase activation. The data shown herealtogether indicate for the first time that AD0157 displays antiangiogenic effects, both invitro and in vivo, that are exerted partly by targeting the Akt signaling pathway in activatedendothelial cells. The fact that these effects are carried out at lower concentrations thanthose required for other inhibitors of angiogenesis makes AD0157 a new promising drugcandidate for further evaluation in the treatment of cancer and other angiogenesis-relatedpathologies. [Our experimental work is supported by grant P12-CTS-1507 (AndalusianGovernment and FEDER) and funds from group BIO-267 (Andalusian Government). The"CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). Thiscommunication has the support of a travel grant "Universidad de Málaga. Campus deExcelencia Internacional Andalucía Tech"].
YR 2014
FD 2014-09-16
LK http://hdl.handle.net/10630/8040
UL http://hdl.handle.net/10630/8040
LA eng
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026