Study for anti-angiogenic activities of polysaccharides isolated from Antrodia cinnamomea in endothelial cells.
The main purposes of this study were to investigate the regulation of polysaccharides isolated from A. cinnamomea on vascular endothelial growth factor (VEGF)-induced cyclin D1 expression and down stream signaling pathway that may correlate with their anti-angiogenc effects in endothelial cells (ECs). Crude and fractionated polysaccharides (Fra-1 to Fra-4) of A. cinnamomea showed slightly toxicity to ECs as compared with their inhibition concentration on angiogenic-related gene expression. The crude extract and fractionated fractions, except for Fra-2, of A. cinnamomea polysaccharides significantly decreased VEGFR2 phosphorylation on tyrosine 1054/1059, cyclin D1 promotor activity, and protein expression induced by VEGF. Crude extract of A. cinnamomea polysaccharides inhibited the binding of VEGF to KDR/flk-1 in a dose-dependent manner. These results indicated that inhibition of VEGF interaction with VEGF receptor 2 is the mechanism serves A. cinnamomea as a protective mechanism composing the anti-angiogenesis function. Furthermore, A. cinnamomea polysaccharides also blocked VEGF-induced migration and capillary-like tube formation of ECs on Matrigel. Taken together, these results indicate that A. cinnamomea polysaccharides inhibit cyclin D1 expression through inhibition of VEGF receptor signaling, leading to the suppression of angiogenesis.
Cheng
Jing-Jy
JJ
National Research Institute of Chinese Medicine, Room 739, No155-1, Section 2, Li-Nung Street, Pei-tou District (112), Taipei, Taiwan.
Huang
Nai-Kuei
NK
Chang
Tun-Tschu
TT
Wang
Danny Ling
DL
Lu
Mei-Kuang
MK
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D005591:Chemical Fractionation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D008518:Medicine, East Asian Traditional; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D020072:Polyporales / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D014443:Tyrosine; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D010936:Plant Extracts; D011134:Polysaccharides; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; D014443:Tyrosine; D040301:Vascular Endothelial Growth Factor Receptor-2