Polyacetylenes function as anti-angiogenic agents.
OBJECTIVE
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.
Wu
Li-Wha
LW
Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China. liwhawu@mail.ncku.edu.tw
Chiang
Yi-Ming
YM
Chuang
Hsiao-Ching
HC
Wang
Sheng-Yang
SY
Yang
Ga-Wen
GW
Chen
Ya-huey
YH
Lai
Ling-Ya
LY
Shyur
Lie-Fen
LF
D000114:Acetylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D031176:Bidens / Q000737:chemistry*; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D053279:Polyynes
D020533:Angiogenesis Inhibitors; D010936:Plant Extracts; D011108:Polymers; D053279:Polyynes; D000114:Acetylene