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A novel function of benzyl isothiocyanate in vascular smooth muscle cells: The role of ERK1/2, cell cycle regulation, and matrix metalloproteinase‐9
Author(s) -
Lee JinYoung,
Moon SungKwon,
Hwang CherWon,
Nam KyungSoo,
Kim YeonKye,
Yoon HoDong,
Kim MinGon,
Kim CheorlHo
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20257
Subject(s) - cyclin dependent kinase , vascular smooth muscle , microbiology and biotechnology , benzyl isothiocyanate , cell cycle , mapk/erk pathway , isothiocyanate , chemistry , matrix metalloproteinase , kinase , cdk inhibitor , cell growth , extracellular matrix , g1 phase , cell cycle checkpoint , cell , biology , biochemistry , endocrinology , smooth muscle
Dietary isothiocyanates (ITCs) have shown protective effects against certain chemically induced cancers in animal models. These inhibitory effects are associated with reduced levels of extracellular signal‐regulated kinase (ERK) 1/2 activity and the arrest of the G 1 cell cycle. Benzyl isothiocyanate (BITC) treatment down‐regulates cyclins and CDKs and up‐regulates the expression of the CDK inhibitor p21, but up‐regulation of p27 or p53 was not detected. Since antiatherogenic effects are not needed for antiproliferation, we determined whether BITC exerted inhibitory effects on matrix metalloproteinase‐9 (MMP‐9) activity in TNF‐α‐induced vascular smooth muscle cells (VSMCs). BITC inhibited TNF‐α‐induced MMP‐9 secretion in VSMC in a dose dependent manner. This inhibition was characterized by the down‐regulation of MMP‐9, which is transcriptionally regulated at the NF‐κB site, and the activation protein‐1 (AP‐1) site in the MMP‐9 promoter. These findings indicate that BITC is an effective agent for inhibiting cell proliferation, the G 1 to S phase cell cycle progress, and MMP‐9 expression through the transcription factors NF‐κB and AP‐1 in TNF‐α‐induced VSMC. © 2004 Wiley‐Liss, Inc.