A novel function of benzyl isothiocyanate in vascular smooth muscle cells: The role of ERK1/2, cell cycle regulation, and matrix metalloproteinase-9

✍ Scribed by Jin-Young Lee; Sung-Kwon Moon; Cher-Won Hwang; Kyung-Soo Nam; Yeon-Kye Kim; Ho-Dong Yoon; Min-Gon Kim; Cheorl-Ho Kim

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 221 KB
• Volume: 203
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20257

✦ Synopsis

Abstract

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.