Andrographolide inhibits human umbilical vein endothelial cell invasion and migration by regulating MMP-2 and MMP-9 during angiogenesis.

ABSTRACT

Angiogenesis, the formation of new blood vessels from preexisting blood vessels, is essential for tumor progression and metastasis. Studies using human umbilical vein endothelial cells clearly demonstrated that administration of andrographolide significantly retarded endothelial cell proliferation, migration, and invasion and tube formation. Gelatin zymographic analysis showed the inhibitory effect of andrographolide on the activation of matrix metalloproteinases MMP-2 and MMP-9. The study reveals that andrographolide treatment could inhibit the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor-κB, and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element­binding protein in B16F-10 melanoma cells. All these results demonstrate that andrographolide inhibits in vitro angiogenesis by inhibiting MMP-2 and MMP-9, and also by regulating the nuclear translocation of transcription factors.