Antiangiogenic activity of low-temperature lysozyme from a marine bacterium <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis> |
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| Authors: | Zhenhua Wang Jincheng Liu Ai Su Mi Sun Chunbo Wang |
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| Institution: | [1]Medical College, Qingdao University, Qingdao 266071, China [2]Yellow Sea Fisheries Research Institute, Chinese Acadetr~V of Fishery Sciences, Qingdao 266071, China |
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| Abstract: | 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. |
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| Keywords: | marine low-temperature lysozyme antiangiogenesis human umbilical vein endothelial cells zebrafish embryo |
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