Angiogenesis is involved in
wound repair and tissue maintenance but is associated with diverse diseases. Pro-angiogenic factors such as
vascular endothelial growth factor (
VEGF) regulate this process. Therefore, searching for treatments to inhibit or promote angiogenesis is attractive. Reports from our group showed that plant
antimicrobial peptides (PAPs) PaDef from avocado and γ-
thionin from habanero pepper are cytotoxic on
cancer cells. However, their functions as angiogenic regulators are unknown. In this work, we evaluate the effect of PaDef and γ-
thionin on the angiogenic processes of two different endothelial cell lines: bovine endothelial cells (BUVEC) and the human endothelial cell line EA.hy926. The results showed that
VEGF (10 ng/mL) stimulated the BUVEC (40 ± 7 %) and EA.hy926 cell proliferation (30 ± 9 %); however,
peptides (5-500 ng/mL) reverted this effect. Besides,
VEGF increased the migration of BUVEC (20 ± 8 %) and EA.hy926 cells (50 ± 6 %), but both PAPs (5 ng/mL) inhibited the
VEGF stimulus (100 %). Furthermore, DMOG 50 μM (an inhibitor of HIF-
hydroxylase) was used in BUVEC and EA.hy926 cells to determine the effect of
hypoxia on
VEGF and
peptide activities. The DMOG reverted the inhibitory action of both
peptides (100 %), indicating that
peptides act through a HIF-independent pathway. Also, the PAPs do not affect the tube formation but decrease it in EA.hy926 cells stimulated with
VEGF (100 %). Additionally, docking assays showed a possible interaction between PAPs and the
VEGF receptor. These results suggest that plant
defensins PaDef and γ-
thionin are potential angiogenic modulators of the
VEGF activity on endothelial cells.