Yuan Liu

Taipei Medical University, Taipei, Taipei, Taiwan

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Publications (4)14.8 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the potential applications of 5,5-diphenyl-2-thiohydantoin-N10 (DPTH-N10) in the treatment of human colon cancer. Subcultured human colon cancer cell line, COLO-205, was used for examining the antiproliferation effect of DPTH-N10 on colon cancer. Thymidine incorporation and cell count were conducted to examine the antiproliferation effect of DPTH-N10. Western blot analysis was performed to examine the protein levels of cell cycle-related proteins. DNA fragmentation assay was performed to examine the occurrence of apoptosis. DPTH-N10 at a range of concentrations (0-30 microM) inhibits the proliferation but did not cause the cell death of COLO-205, indicating that it may have an inhibitory effect on the cell proliferation in COLO-205. The apoptosis was observed in COLO-205 when the DPTH-N10 concentrations were higher than 30 muM. Western blot analysis showed that the protein level of the cell cycle inhibitory protein, p21, in COLO-205 increased after DPTH-N10 treatment. Immunoprecipitation showed that the formation of the cyclin-dependent kinase (CDK)2-p21 complex was increased in the DPTH-N10-treated COLO-205. Kinase assay further demonstrated that the CDK2 activity was decreased in the DPTH-N10-treated COLO-205. DPTH-N10 caused growth inhibition in COLO-205 by inhibiting DNA synthesis and activating apoptosis. The findings from our previous in vitro studies in DPTH-N10-induced anti-angiogenic effect and from the present in vitro studies in DPTH-N10-induced antiproliferation effect on colon cancer cell line strongly suggest the potential applications of DPTH-N10 in the treatment of human colon cancer.
    Archiv für Experimentelle Pathologie und Pharmakologie 07/2010; 382(1):43-50. · 2.15 Impact Factor
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    ABSTRACT: Previously, we demonstrated that 5,5-diphenyl-2-thiohydantoin (DPTH) exerts an anti-proliferation effect on subcultured human umbilical vein endothelial cells (HUVEC). In the present study, we show that 2(naphthalen-2-ylmethylsulfanyl)-5,5-diphenyl-1,5-dihydro-imidazol-4-one (DPTH-N10), a derivative compound of DPTH, exerts a 5 times stronger inhibition of [3H]thymidine incorporation into HUVEC as compared with DPTH and at very low concentrations (0-20 microM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a concentration- and time-dependent manner, but not in human fibroblasts. [3H]thymidine incorporation analysis demonstrated that treatment of HUVEC with DPTH-N10 arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed that the protein level of p21 in HUVEC increased after DPTH-N10 treatment. In contrast, the protein levels of p27, p53, cyclins A, D1, D3 and E, cyclin-dependent kinase (CDK)2, and CDK4 in HUVEC were not changed significantly after DPTH-N10 treatment. Immunoprecipitation showed that the formation of the CDK2-p21 complex, but not the CDK2-p27, CDK4-p21, and CDK4-p27 complex, was increased in the DPTH-N10-treated HUVEC. Kinase assay further demonstrated that CDK2, but not CDK4, kinase activity was decreased in the DPTH-N10-treated HUVEC. Pretreatment of HUVEC with a p21, but not p27, antisense oligonucleotide reversed the DPTH-N10-induced inhibition of [3H]thymidine incorporation into HUVEC. Taken together, these data suggest that DPTH-N10 inhibits HUVEC proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 kinase activity, and finally interrupts the cell cycle. Capillary-like tube formation, aortic ring culture, and chick embryo chorioallantoic membrane (CAM) assays further demonstrated the anti-angiogenic effect of DPTH-N10.
    Cancer letters 11/2008; 271(2):294-305. · 4.86 Impact Factor
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    ABSTRACT: Previously, we identified DPTH, an analogue of antiepileptic drug phenytoin (5,5-diphenylhydantoin, DPT), capable of retarding the cell cycle in the human vascular endothelial cells. Our data suggest that DPTH inhibits human umbilical venous endothelial cells (HUVEC) proliferation by increasing the level of p21 protein, which in turn inhibits the activities of cyclin-dependent kinase (CDK)2 and CDK4, and finally interrupts the cell cycle. To search chemicals with more potency in anti-angiogenic activity, we designed and synthesized several chemical compounds based on the structure-activity relationship consideration. We evaluated the anti-angiogenic activity of these compounds by examining their effects on DNA synthesis, cell number, p21 induction and capillary-like tube formation. Our results showed that introduction of side chain containing an aromatic ring structure with right spatial arrangement at sulfur atom of DPTH enhanced the anti-angiogenic activity in HUVEC.
    Vascular Pharmacology 01/2008; 48(2-3):138-42. · 3.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to examine the anti-proliferation effect of 5,5-diphenyl-2-thiohydantoin (DPTH), an analogue of antiepileptic drug phenytoin (5,5-diphenylhydantoin), on human umbilical vein endothelial cells (HUVEC) and its possible molecular mechanism underlying. Here we demonstrated that DPTH at a range of concentrations (12.5-50 microM) dose- and time-dependently inhibited DNA synthesis and decreased cell number in cultured HUVEC, but not human fibroblasts. DPTH was not cytotoxic at these concentrations. [3H]Thymidine incorporation and flow cytometry analyses demonstrated that treatment of HUVEC with DPTH arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed that the protein level of p21 increased after DPTH treated. In contrast, the protein levels of p27, p53, cyclins A, D1, D3 and E, cyclin-dependent kinase (CDK)2, and CDK4 in HUVEC were not changed significantly after DPTH treatment. Immunoprecipitation showed that the formations of the CDK2-p21 and CDK4-p21 complex, but not the CDK2-p27 and CDK4-p27 complex, were increased in the DPTH-treated HUVEC. Kinase assay further demonstrated that both CDK2 and CDK4 kinase activities were decreased in the DPTH-treated HUVEC. Pretreatment of HUVEC with a p21 antisense oligonucleotide reversed the DPTH-induced inhibition of [3H]thymidine incorporation into HUVEC. In conclusion, these data suggest that DPTH inhibits HUVEC proliferation by increasing the level of p21 protein, which in turn inhibits CDK2 and CDK4 kinase activities, and finally interrupts the cell cycle. The findings from the present study suggest that DPTH might have the potential to inhibit the occurrence of angiogenesis.
    Biochemical Pharmacology 02/2004; 67(1):67-75. · 4.58 Impact Factor

Publication Stats

9 Citations
14.80 Total Impact Points

Institutions

  • 2004–2010
    • Taipei Medical University
      • • Graduate Institute of Medical Sciences
      • • School of Medicine
      Taipei, Taipei, Taiwan
  • 2008
    • Fu Jen Catholic University
      • School of Medicine
      Taipei, Taipei, Taiwan