Antiangiogenic effect of bile acid acylated heparin derivative

Kyeongsoon Park, Yoo Shin Kim, Gee Young Lee, Ju Ock Nam, Seok Ki Lee, Rang Woon Park, Sang Yoon Kim, In San Kim, Youngro Byun

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Purpose. Chemically modified heparin-DOCA was prepared and found to have markedly lower anticoagulant activity than heparin. In the present study, we elucidated the antiangiogenic and antitumoral activities of heparin-DOCA derivative. Methods. To evaluate the antiangiogenic and antitumoral effects of heparin-DOCA, capillary-like tube formation assay, Matrigel plug assay in vivo, western blotting for FGFR phosphorylation, ERK and p38 MAPK activities, tumor growth of SCC in vivo and immunostaining of blood vessels in tumor tissues were performed. Results. Heparin-DOCA inhibited capillary-like tubular structures of endothelial cells and bFGF-induced neovascularizations in Matrigel plug assays. Signaling experiments showed that heparin-DOCA significantly inhibited angiogenesis by suppressing the phosphorylation of FGFR and its downstream signal pathways (ERK and p38 MAPK activities). The antiangiogenic activity of this heparin derivative was found to be closely associated with antitumoral activity in a mouse model. In addition, histological evaluations supported the inhibitory effect of heparin-DOCA on blood vessel formation in tumor tissues. Conclusion. Heparin-DOCA derivative exerted a significant antitumoral effect by inhibiting angiogenesis resulting from the disruption of FGF/FGFR and its downstream signal pathways, and could be applied to treat various angiogenic diseases.

Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalPharmaceutical research
Issue number1
Publication statusPublished - 2007 Jan
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Next generation New Technology Development Program of the Korean Ministry of Commerce, Industry, and Energy (Grant No. #10011353).


  • Antiangiogenesis
  • HUVECs
  • Heparin
  • Heparin-DOCA
  • SCC

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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