We extracted marine low-temperature lysozyme (MLTL),a novel lysozyme,from a marine microorganism through fermentation.Our previous study suggested that a low molecular weight (16 kDa) may exert anti-tumor activity thr...We extracted marine low-temperature lysozyme (MLTL),a novel lysozyme,from a marine microorganism through fermentation.Our previous study suggested that a low molecular weight (16 kDa) may exert anti-tumor activity through antiangiogenesis.In this study,we extracted a high weight (39 kDa) and investigated its antiangiogenic activity in vivo and in vitro.Using zebrafish embryos as an in vivo study model,we found that treatment with MLTL significantly inhibited the growth of subintestinal vessels (SIVs) in a dose-dependent manner and that 400 μg/ml MLTL was sufficient to block the growth of SIVs.An in vitro study conducted using human umbilical vein endothelial cells (HUVECs) revealed that MLTL suppressed the proliferation,migration and tube formation of HUVECs in a dose-dependent manner.Interestingly,assays by flow cytometry and DNA electrophoresis indicated that MLTL was able to induce apoptosis of HUVECs.Moreover,further study demonstrated that the disruption of intracellular Ca2+ homeostasis may play an important role in MLTL induced apoptosis of HUVECs.Taken together,the results of this study demonstrate for the first time that MLTL inhibits angiogenesis through its pleiotropic effects on vascular endothelial cells and induces apoptosis through regulation of cellular Ca2+ levels.The results of this study also revealed a possible mechanism underlying the antiangiogenic effect of MLTL and suggested that MLTL may be a promising new antiangiogenic agent for use in cancer therapy.展开更多
基金Supported by the National High Technology Research and Development Program (863 Program) (No.2003AA625070)the Research Fund Program of Qingdao University (No.20051102)
文摘We extracted marine low-temperature lysozyme (MLTL),a novel lysozyme,from a marine microorganism through fermentation.Our previous study suggested that a low molecular weight (16 kDa) may exert anti-tumor activity through antiangiogenesis.In this study,we extracted a high weight (39 kDa) and investigated its antiangiogenic activity in vivo and in vitro.Using zebrafish embryos as an in vivo study model,we found that treatment with MLTL significantly inhibited the growth of subintestinal vessels (SIVs) in a dose-dependent manner and that 400 μg/ml MLTL was sufficient to block the growth of SIVs.An in vitro study conducted using human umbilical vein endothelial cells (HUVECs) revealed that MLTL suppressed the proliferation,migration and tube formation of HUVECs in a dose-dependent manner.Interestingly,assays by flow cytometry and DNA electrophoresis indicated that MLTL was able to induce apoptosis of HUVECs.Moreover,further study demonstrated that the disruption of intracellular Ca2+ homeostasis may play an important role in MLTL induced apoptosis of HUVECs.Taken together,the results of this study demonstrate for the first time that MLTL inhibits angiogenesis through its pleiotropic effects on vascular endothelial cells and induces apoptosis through regulation of cellular Ca2+ levels.The results of this study also revealed a possible mechanism underlying the antiangiogenic effect of MLTL and suggested that MLTL may be a promising new antiangiogenic agent for use in cancer therapy.
