The induction of angiogenesis is a crucial step in
tumor progression, and therefore, efficient inhibition of angiogenesis is considered a powerful strategy for the treatment of
cancer. In the present study, we report that the lipophilic
antimicrobial peptides from EML-CAP3, a new endophytic bacterial strain isolated from red pepper leaf (Capsicum annuum L.), exhibit potent antiangiogenic activity both in vitro and in vivo. The newly obtained
antimicrobial peptides effectively inhibited the proliferation of human umbilical vein endothelial cells at subtoxic doses. Furthermore, the
peptides suppressed the in vitro characteristics of angiogenesis such as endothelial cell invasion and tube formation stimulated by
vascular endothelial growth factor, as well as neovascularization of the chorioallantoic membrane of growing chick embryos in vivo without showing cytotoxicity. Notably, the
angiostatic peptides blocked
tumor cell-induced angiogenesis by suppressing the expression levels of
hypoxia-inducible factor-1α and its target gene,
vascular endothelial growth factor (
VEGF). To our knowledge, our findings demonstrate for the first time that the
antimicrobial peptides from EML-CAP3 possess antiangiogenic potential and may thus be used for the treatment of hypervascularized
tumors.