Polyacetylenes Function as Anti-Angiogenic Agents

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.