title: 2-Hydroxy-3,4-naphthochalcone (2H-NC) inhibits TNFα-induced tumor invasion through the downregulation of NF-κB-mediated MMP-9 gene expression.
abstract: The control of tumor metastasis is important for the successful prevention and treatment of cancer. Emerging evidence indicates that various natural and synthetic chalcones exhibit antimetastatic activity through the inhibition of nuclear factor-κB (NF-κB), although the precise mechanism by which this occurs is currently unclear. In this study, 2-hydroxy-3,4-naphthochalcone (2H-NC) was found to reduce tumor necrosis factor alpha (TNFα)-induced MMP-9 mRNA expression and gelatinolytic enzyme activity. These actions were associated with inhibition of RelA/p65 NF-κB activity. In addition, 2H-NC inhibited TNFα-induced invasion of MDA-MB-231 breast cancer cells, as assessed using a three-dimensional spheroid invasion assay. Taken together, these data demonstrate that 2H-NC prevents TNFα-induced tumor cell invasion through downregulation of NF-κB-mediated MMP-9 gene expression, and thereby identify naphthochalcones as a potentially effective class of molecules to use as a platform for the development of antimetastatic agents.
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Mi So
authors.initials: MS
authors.lastname: Lee
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Koh
authors.forename: Geum Soog
authors.initials: GS
authors.lastname: Kim
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Lee
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Noh
authors.forename: Seung Yu
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D009281:Naphthalenes / Q000737:chemistry* / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000633:toxicity
chemical_list: D047188:Chalcones; D016328:NF-kappa B; D009281:Naphthalenes; D014409:Tumor Necrosis Factor-alpha; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9