Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ), bee pollen, and Chinese red propolis] from the honeybee, Apis mellifera, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs).


METHODS
In an in vitro tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE)]. To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE.


RESULTS
RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced in vitro tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation.


CONCLUSIONS
Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.
Izuta
Hiroshi
H
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan. hizuta@hotmail.com
Shimazawa
Masamitsu
M
Tsuruma
Kazuhiro
K
Araki
Yoko
Y
Mishima
Satoshi
S
Hara
Hideaki
H
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D056705:Apitherapy; D001516:Bees; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects*; D005227:Fatty Acids / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011058:Pollen; D011429:Propolis / Q000737:chemistry / Q000494:pharmacology*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D000099219:Royal Jelly
D020533:Angiogenesis Inhibitors; D002109:Caffeic Acids; D005227:Fatty Acids; D010626:Phenylethyl Alcohol; D011429:Propolis; D042461:Vascular Endothelial Growth Factor A; D000099219:Royal Jelly; C055494:caffeic acid phenethyl ester