Anti-angiogenesis effect of beta-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model

作者:Rastegari Pouyani Mohsen; Mostafaie Ali*; Mansouri Kamran; Mortazavi Jahromi Seyed Shahabeddin; Mohammadi Motlagh Hamid Reza; Mirshafiey Abbas*
来源:Clinical and Experimental Pharmacology and Physiology, 2018, 45(4): 370-376.
DOI:10.1111/1440-1681.12907

摘要

Angiogenesis is a process through which new capillaries are formed from pre-existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The -D-mannuronic acid (M2000) is a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti-angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti-proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen-cytodex model and the chickchorioallantoic membrane(CAM) assay were then used to evaluate the anti-angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100 mu g/mL) had no cytotoxic effect on human umbilical vein endothelial cells(HUVECs). It was also illustrated that M2000 had little or no anti-proliferative effect on HUVECs. In addition, the anti-angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose-dependent in the in vivo status. This study showed that M2000 could be considered as an anti-angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti-inflammatory effects may partly be attributable to its anti-angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis-related disorders.

  • 出版日期2018-4