BACKGROUND: TZT-1027 (Soblidotin), a microtubule-depolymerizing agent, has antivascular activity which disrupts newly formed tumor vasculature. In this study, it was investigated whether TZT-1027 has also antiangiogenic activity preventing neovascularization. MATERIALS AND METHODS: Antiangiogenic activities were evaluated in vivo in a chick embryo chorioallantoic membrane (CAM) assay and in vitro in a tube formation assay on human umbilical vein endothelial cells (HUVEC). RT-PCR and skimmed milk zymography analyses were performed to clarify the involvement of angiogenesis-related proteolytic enzymes and transcription factors. RESULTS: TZT-1027 at doses of 0.01 and 0.06 microg/egg showed potent antiangiogenic activities in the CAM assay (80% and 100% inhibition, respectively), with no lethal toxicity to the chick embryo. TZT-1027 at doses of 0.01-10 ng/mL prevented tube formation, while 1-100 ng/mL disrupted the preformed vascular tube. However, mRNA and protein expression were unchanged. CONCLUSION: TZT-1027 showed antiangiogenic activity at lower doses than it exhibited its antivascular activity. We believe it would exert its antiangiogenic activity, even if kept in a tumor at reduced concentrations to keep its antivascular activity to a minimum.
BACKGROUND:TZT-1027 (Soblidotin), a microtubule-depolymerizing agent, has antivascular activity which disrupts newly formed tumor vasculature. In this study, it was investigated whether TZT-1027 has also antiangiogenic activity preventing neovascularization. MATERIALS AND METHODS: Antiangiogenic activities were evaluated in vivo in a chick embryo chorioallantoic membrane (CAM) assay and in vitro in a tube formation assay on human umbilical vein endothelial cells (HUVEC). RT-PCR and skimmed milk zymography analyses were performed to clarify the involvement of angiogenesis-related proteolytic enzymes and transcription factors. RESULTS:TZT-1027 at doses of 0.01 and 0.06 microg/egg showed potent antiangiogenic activities in the CAM assay (80% and 100% inhibition, respectively), with no lethal toxicity to the chick embryo. TZT-1027 at doses of 0.01-10 ng/mL prevented tube formation, while 1-100 ng/mL disrupted the preformed vascular tube. However, mRNA and protein expression were unchanged. CONCLUSION:TZT-1027 showed antiangiogenic activity at lower doses than it exhibited its antivascular activity. We believe it would exert its antiangiogenic activity, even if kept in a tumor at reduced concentrations to keep its antivascular activity to a minimum.