Study for anti-angiogenic activities of polysaccharides isolated from Antrodia cinnamomea in endothelial cells

• Published in: Life sciences (1973) Vol. 76; no. 26; pp. 3029 - 3042
• Main Authors: Cheng, Jing-Jy, Huang, Nai-Kuei, Chang, Tun-Tschu, Ling Wang, Danny, Lu, Mei-Kuang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 13.05.2005
• Subjects: Angiogenesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Animals; Antrodia cinnamomea; Aorta - cytology; Aorta - drug effects; Cattle; Cells, Cultured; Chemical Fractionation; Cyclin D1; Cyclin D1 - genetics; Cyclin D1 - metabolism; Dose-Response Relationship, Drug; Endothelial cell; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Medicine, East Asian Traditional; Phosphorylation; Plant Extracts - pharmacology; Polyporales - chemistry; Polysaccharide; Polysaccharides - chemistry; Polysaccharides - pharmacology; Promoter Regions, Genetic; Tube formation; Tyrosine; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGF; Angiogenesis; Endothelial cell; VEGF; Tube formation; Cyclin D1; Polysaccharide; Antrodia cinnamomea
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2004.11.023

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.