Effects of Tubulyzines, Novel Microtubule-Binding Triazine Molecules, on Endothelial Progenitor Cell Differentiation

  • Park, Hyo-Eun (Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea) ;
  • Lee, Soo-Young (Department of Natural Sciences, College of Medicine, The Catholic University of Korea) ;
  • Ahn, Hyun-Young (Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, The Catholic University of Korea) ;
  • Shin, Jong-Cheol (Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, The Catholic University of Korea) ;
  • Chang, Young-Tae (Department of Chemistry, New York University) ;
  • Joe, Young-Ae (Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea)
  • 발행 : 2003.06.01

초록

Microtubule-binding molecules have been developed as anti-cancer agents to overcome the toxicities of current chemotherapeutics and also have potential for use as anti-angiogenic agents. In this work, we examined the effect of novel triazine compounds, Tubulyzines (microTUBUle LYsing triaZINE), derived from the orthogonal synthesis of a triazine library, on endothelial progenitor cell differentiation. When mononuclear cells isolated from human cord blood were cultured on fibronectin-coated plates for 7 days, all the Tubulyzine compounds A, B, and C (TA, TB, and TC) tested decreased the number of adherent cells in a dose-dependent manner in a coo. centration ranges of 2-5 to $80\mu\textrm{M}$. TA ($IC_{50}$=$20\mu\textrm{M}$) showed slightly more potent activity than TB and TC. Adherent cells treated with TA also exhibited a lower level of ability to ac-LDL uptake, with low ratios of positive cells out of total adherent cells, in a dose-dependent manner and weak expression of endothelial lineage markers, KDR, CD31, and vWF at $20\mu\textrm{M}$. Therefore, these results suggest that tubulyzine A (TA) can be effectively used for the inhibition of new vessel growth by inhibiting differentiation of endothelial progenitor cells.

키워드

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