Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

Toxicol Appl Pharmacol. 2005 Dec 1;209(2):105-13. doi: 10.1016/j.taap.2005.04.010. Epub 2005 Jun 13.

Abstract

A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependent manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables.

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Brassica* / chemistry
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Carcinogens
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Collagen
  • Drug Combinations
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Female
  • Formazans / chemistry
  • Humans
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology
  • L-Lactate Dehydrogenase / metabolism
  • Laminin
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Nasturtium* / chemistry
  • Plant Extracts / pharmacology*
  • Proteoglycans
  • Tetradecanoylphorbol Acetate
  • Tetrazolium Salts / chemistry
  • Thiocyanates / chemistry
  • Thiocyanates / pharmacology

Substances

  • 7-methylsulfinylheptyl isothiocyanate
  • Anticarcinogenic Agents
  • Carcinogens
  • Drug Combinations
  • Formazans
  • Isothiocyanates
  • Laminin
  • Matrix Metalloproteinase Inhibitors
  • Plant Extracts
  • Proteoglycans
  • Tetrazolium Salts
  • Thiocyanates
  • matrigel
  • MTT formazan
  • Collagen
  • L-Lactate Dehydrogenase
  • Matrix Metalloproteinase 9
  • sulforafan
  • Tetradecanoylphorbol Acetate