Gambogic amide inhibits angiogenesis by suppressing VEGF/VEGFR2 in endothelial cells in a TrkA-independent manner.
Pharm Biol
; 59(1): 1566-1575, 2021 Dec.
Article
in En
| MEDLINE
| ID: mdl-34767490
ABSTRACT
CONTEXT Gambogic amide (GA-amide) is a non-peptide molecule that has high affinity for tropomyosin receptor kinase A (TrkA) and possesses robust neurotrophic activity, but its effect on angiogenesis is unclear. OBJECTIVE:
The study investigates the antiangiogenic effect of GA-amide on endothelial cells (ECs). MATERIALS ANDMETHODS:
The viability of endothelial cells (ECs) treated with 0.1, 0.15, 0.2, 0.3, 0.4, and 0.5 µM GA-amide for 48 h was detected by MTS assay. Wound healing and angiogenesis assays were performed on cells treated with 0.2 µM GA-amide. Chicken eggs at day 7 post-fertilization were divided into the dimethyl sulfoxide (DMSO), bevacizumab (40 µg), and GA-amide (18.8 and 62.8 ng) groups to assess the antiangiogenic effect for 3 days. mRNA and protein expression in cells treated with 0.1, 0.2, 0.4, 0.8, and 1.2 µM GA-amide for 6 h was detected by qRT-PCR and Western blots, respectively.RESULTS:
GA-amide inhibited HUVEC (IC50 = 0.1269 µM) and NhEC (IC50 = 0.1740 µM) proliferation, induced cell apoptosis, and inhibited the migration and angiogenesis at a relatively safe dose (0.2 µM) in vitro. GA-amide reduced the number of capillaries from 56 ± 14.67 (DMSO) to 20.3 ± 5.12 (62.8 ng) in chick chorioallantoic membrane (CAM) assay. However, inactivation of TrkA couldn't reverse the antiangiogenic effect of GA-amide. Moreover, GA-amide suppressed the expression of VEGF and VEGFR2, and decreased activation of the AKT/mTOR and PLCγ/Erk1/2 pathways.CONCLUSIONS:
Considering the antiangiogenic effect of GA-amide, it might be developed as a useful agent for use in clinical combination therapies.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Angiogenesis Inhibitors
/
Endothelial Cells
/
Xanthones
Limits:
Animals
/
Humans
Language:
En
Journal:
Pharm Biol
Year:
2021
Document type:
Article
Affiliation country:
China