The novel model peptide, αAL14, regulates angiogenesis by inhibiting VEGFR 2-mediated signaling in HUVECs

Abstract

Inhibition of angiogenesis has been focused on as a strategy for treating several diseases including cancer. In this study, a novel model peptide αAL14 was synthesized and used to identify its inhibitory effects on angiogenesis. The anti-angiogenic effects of αAL14 were investigated using vascular endothelial cells, HUVECs. αAL14 inhibited critical angiogenic processes including tubule formation, cell migration and cell invasion with no influence on cell proliferation in HUVECs. Activity of VEGFR2 was inhibited by αAL14 treatment in HUVECs. Additionally, activities of major subsequent downstream factors of VEGFR2 such as ERK, FAK and Akt were decreased. αAL14 affected expression of Rac1, Cdc42, Arp2 and WAVE2 which are involved in formation of lamellipodia. Moreover, αAL14 reduced NF-κB that can promote expression of several genes relating to cell invasion such as MMP2 and MMP9. Therefore, the results suggest that αAL14 has a potential to be developed as anti-angiogenic drug for treating diseases driven by abnormal angiogenesis.

Antimicrobial and antitumor properties of anuran peptide temporin-SHf induce apoptosis in A549 lung cancer cells

“…As like, an amphibian Chan Su peptide inhibited the protein expression of VEGF165 and Ras, exerting anti-angiogenic effects by suppressing the VEGF165-VEGFR2-Ras signaling pathway (Xia et al 2019 ). The αAL14, a synthetic peptide, inhibits tube formation in HUVEC by suppressing the activity of VEGFR2 (Kim et al 2016 ). Temporin-1CEa was found to prevent the formation of VEGF in human melanoma A375 cells, thus inhibiting the formation of new blood vessels at an IC 50 value of 18.2 μM (Wang et al 2016 ).…”