Anti-angiogenic potential of a cancer chemopreventive flavonoid antioxidant, silymarin: Inhibition of key attributes of vascular endothelial cells and angiogenic cytokine secretion by cancer epithelial cells

Cheng Jiang, Rajesh Agarwal, Junxuan Lü

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Abstract

In recent studies, we have shown that silymarin, a naturally occurring flavonoid antioxidant, exhibits anti-cancer effects against several epithelial cancers. Here, we assessed its potential as an anti-angiogenic agent employing human umbilical vein endothelial cells (HUVEC) and human prostate and breast cancer epithelial cells. When sub-confluent HUVEC were treated for 48 h, adherent cell number decreased by 50 and 90% at 50 and 100 μg/ml doses, respectively. Apoptotic cell death principally accounted for cell loss at >50 μg/ml doses. In biochemical analysis, silymarin treatment of HUVEC for 6 h resulted in a concentration-dependent decrease in the secretion and cellular content of matrix metalloproteinase (MMP)-2/gelatinase A. Silymarin also inhibited HUVEC tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel. In other studies, 5 to 6 h exposure of DU145 prostate, and MCF-7 and MDA-MB-468 breast cancer cells to silymarin resulted in a dose-dependent decrease in the secreted vascular endothelial growth factor (VEGF) level in conditioned media without any visible change in cell morphology. The inhibitory effect of silymarin on VEGF secretion occurred as early as 1 h. These observations indicate a rapid inhibitory action of silymarin on the secretion of this primary angiogenic cytokine by cancer epithelial cells. Taken together, the results of this study support the hypothesis that silymarin possesses an anti-angiogenic potential that may critically contribute to its cancer chemopreventive efficacy. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)371-378
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume276
Issue number1
DOIs
Publication statusPublished - Sep 16 2000

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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