Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells.
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.
Rose
Peter
P
Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore. bchpcr@nus.edu.sg
Huang
Qing
Q
Ong
Choon Nam
CN
Whiteman
Matt
M
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001937:Brassica / Q000737:chemistry; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D002273:Carcinogens; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005260:Female; D005562:Formazans / Q000737:chemistry; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007797:Laminin; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D031223:Nasturtium / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D011509:Proteoglycans; D013454:Sulfoxides; D013755:Tetradecanoylphorbol Acetate; D013778:Tetrazolium Salts / Q000737:chemistry; D013861:Thiocyanates / Q000737:chemistry / Q000494:pharmacology
C416762:7-methylsulfinylheptyl isothiocyanate; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004338:Drug Combinations; D005562:Formazans; D017879:Isothiocyanates; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D011509:Proteoglycans; D013454:Sulfoxides; D013778:Tetrazolium Salts; D013861:Thiocyanates; C059485:matrigel; C079782:MTT formazan; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D020780:Matrix Metalloproteinase 9; C016766:sulforaphane; D013755:Tetradecanoylphorbol Acetate