title: Modifying effects of dietary factors on (-)-epigallocatechin-3-gallate-induced pro-matrix metalloproteinase-7 production in HT-29 human colorectal cancer cells.
abstract: (-)-Epigallocatechin-3-gallate (EGCG), one of the main constituents of green tea, has been reported to function as an antioxidant with chemopreventive potential. In contrast, we have recently reported that EGCG enhanced pro-matrix metalloproteinase (MMP)-7 in HT-29 human colon cancer cells via spontaneous superoxide generation. In the present study, we examined the effects of dietary antioxidants on both spontaneous and EGCG-upregulated proMMP-7 production in HT-29 cells. Benzyl isothiocyanate (BITC), curcumin (CUR), gallic acid (GA), and N-acetyl-L-cysteine (NAC) reduced that production, while each alone did not have any effect on spontaneous production. None of the dietary factors suppressed EGCG-induced hydrogen peroxide generation in the media tested, whereas BITC, GA, and NAC inhibited the EGCG-enhanced activator protein (AP)-1 transcription activity by 126%, 77%, and 97%, respectively. Although CUR abolished the EGCG-upregulated MMP-7 mRNA expression, it unexpectedly enhanced the AP-1 activity by 502%, suggesting that this factor may disrupt the MMP-7 mRNA stabilization process. Together, our results indicate that dietary antioxidants modulate EGCG-induced MMP-7 production through different mechanisms.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan.
authors.forename: Mihye
authors.initials: M
authors.lastname: Kim
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohigashi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000178:diet therapy / Q000188:drug therapy*; D003470:Culture Media / Q000032:analysis / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology; D005707:Gallic Acid / Q000494:pharmacology; D017930:Genes, Reporter; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D017879:Isothiocyanates / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003470:Culture Media; D017879:Isothiocyanates; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D005707:Gallic Acid; C031403:benzyl isothiocyanate; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D008156:Luciferases; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D003474:Curcumin; D000111:Acetylcysteine