Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway

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Title:	Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway
Authors:	賴光啟;LAI, KUANG-CHI;黃安正;HUANG, AN-CHENG;徐素琴;HSU, SHU-CHUN;郭昭麟;KUO, CHAO-LIN;楊家欣;YANG, JAI-SING;吳莘華;SHIN-HWAR, WU;鍾景光;Chung, Jing-Gung
Contributors:	生物科技學系
Keywords:	BITC;migration;invasion;MMP2;MMP9;human colon cancer HT29 cells
Date:	2010-03
Issue Date:	2012-11-23 09:12:38 (UTC+0)
Abstract:	Benzyl isothiocyanate (BITC), a component of dietary cruciferous vegetables, has antioxidant and anticancer properties. In this study, we show for the first time the antimetastatic effects of BITC in human colon cancer HT29 cells. BITC had an inhibitory effect on cell migration and invasion. Protein levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinaseplasminogen activator (u-PA) were reduced by BITC in a concentration-dependent manner. BITC also exerted an inhibitory effect on phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2), extracellular signal-regulated kinases 1 and 2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) that are upstream of nuclear factor kappa B (NF-κB). BITC inhibited DNA binding activity of NF-κB. Moreover, BITC decreased the levels of c-Fos, c-Jun, Ras, FAK, PI3K and GRB2 in HT29 cells. Reductions in the enzyme activity, protein and mRNA (mRNA) levels of MMP-2 were observed in BITC-treated HT29 cells. BITC also inhibited mRNA levels of MMP-2, -7, and -9 in HT29 cells. Results from zymography showed that BITC treatment decreased MMP-2 expression in a concentration-dependent manner. BITC inhibited PKCδ activity in HT29 cells. Furthermore, inhibitors specific for JNK (SP600125) reduced expression of MMP-2, MMP-9, and u-PA. These results demonstrated that BITC could alter HT29 cell metastasis by reduction of MMP-2, MMP-9, and u-PA expression through the suppression of a PKC, MAPK signaling pathway and inhibition of NF-κB levels. These findings suggest that BITC has potential as an antimetastatic agent.
Relation:	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Appears in Collections:	[Department of Biotechnology] Journal Article

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