TY - JOUR
T1 - Polyacetylenes function as anti-angiogenic agents
AU - Wu, Li Wha
AU - Chiang, Yi Ming
AU - Chuang, Hsiao Ching
AU - Wang, Sheng Yang
AU - Yang, Ga Wen
AU - Chen, Ya Huey
AU - Lai, Ling Ya
AU - Shyur, Lie Fen
N1 - Funding Information:
This work was supported in part by a 3-year career development grant (EX-909016BC) from National Research Health Institute and from Academia Sinica, Taiwan, Republic of China.
PY - 2004
Y1 - 2004
N2 - 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 μg/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 μg/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.
AB - 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 μg/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 μg/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.
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U2 - 10.1023/B:PHAM.0000048204.08865.41
DO - 10.1023/B:PHAM.0000048204.08865.41
M3 - Article
C2 - 15587935
AN - SCOPUS:21644437806
SN - 0724-8741
VL - 21
SP - 2112
EP - 2119
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 11
ER -