Polyacetylenes function as anti-angiogenic agents

• Published in: Pharmaceutical research 2004-11, Vol.21 (11), p.2112-2119
• Main Authors: Wu, Li-Wha, Chiang, Yi-Ming, Chuang, Hsiao-Ching, Wang, Sheng-Yang, Yang, Ga-Wen, Chen, Ya-huey, Lai, Ling-Ya, Shyur, Lie-Fen
• Format: Article
• Language: English
• Subjects: Acetylene - analogs & derivatives; Acetylene - chemistry; Acetylene - pharmacology; Angiogenesis; Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - pharmacology; Apoptosis - drug effects; Bidens - chemistry; Blotting, Western; Cancer; Cell cycle; Cell growth; Cell Line; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Endothelial Cells - drug effects; Endothelium; Fibroblasts; Flow Cytometry; Growth factors; Humans; Keratinocytes - drug effects; Magnetic Resonance Spectroscopy; Microtubules - drug effects; NMR; Nuclear magnetic resonance; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polymers - chemistry; Polymers - pharmacology; Polyynes; Veins & arteries
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/B:PHAM.0000048204.08865.41

To investigate the antiangiogenic effects of plant extracts and polyacetylenes isolated from Bidens pilosa Linn., which is a popular nutraceutical herbal tea and folk medicine in anti-inflammatory, antitumor, and other medications worldwide. Anti-cell proliferation, anti-tube formation, and cell migration assays were used for the valuation of bioactivities of target plant extracts and phytocompounds against angiogenesis. Bioactivity-guided fractionation, HPLC, and various spectral analyses were used to identify active fraction and phytocompounds for anti-angiogenesis. We show that an ethyl acetate (EA) fraction of B. pilosa exhibited significant anti-cell proliferation and anti-tube formation activities against human umbilical vein endothelium cells (HUVEC). Bioassay-guided fractionation led to isolation of one new and one known polyacetylenes, 1,2-dihydroxytrideca-5,7,9,11-tetrayne (1) and 1,3-dihydroxy-6(E)- tetradecene-8,10,12-triyne (2), respectively, from the EA fraction. Compounds 1 and 2 manifested highly specific and significant activities against HUVEC proliferation with IC50 values of 2.5 and 0.375 microg/ml, respectively, however, compound 1 had a more potent effect on preventing tube formation of HUVEC than compound 2 at a dose of 2.5 microg/ml. Western blot analysis showed that both compounds upregulated p27(Kip) or p21(Cip1), cyclin-dependent kinase inhibitors, in HUVEC. This is the first report to demonstrate that polyacetylenes possess significant anti-angiogenic activities and the ability to regulate the expression of cell cycle mediators, for example, p27(Kip1), p21(Cip1), or cyclin E.