title: A small compound that inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-9 upregulation.
abstract: Matrix metalloproteinase-9 (MMP-9) is critically involved in the tumor invasion and metastasis processes. Since TNF-alpha plays a crucial role in the regulation of MMP-9 expression, the development of molecules capable of modulating TNF-alpha-induced signaling is an issue of concern. We identified a novel synthetic compound that inhibits TNF-alpha-induced MMP-9 upregulation in the HT1080 human fibrosarcoma cell line. The active compound SM-7368 inhibited TNF-alpha-induced MMP-9 upregulation in a concentration-dependent manner and showed maximal activity at 10 microM. SM-7368 inhibited TNF-alpha-induced MMP-9 mRNA transcript accumulation and protein expression. We also found that SM-7368 strongly inhibits TNF-alpha-induced NF-kappaB activity but not AP-1 activity. Moreover, we found that SM-7368 strongly inhibits the TNF-alpha-induced invasion of HT1080 human fibrosarcoma cell line. Taken together, our results demonstrate that SM-7368 is a synthetic compound that inhibits TNF-alpha-induced MMP-9 expression, and thus SM-7368 should be useful for the development of chemotherapies targeting TNF-alpha-mediated tumor invasion and metastasis.
authors.affiliation: Medical Research Center for Cancer Molecular Therapy and Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Kyoung Sun
authors.initials: KS
authors.lastname: Park
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Taehoon
authors.initials: T
authors.lastname: Lee
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Woo
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D001549:Benzamides / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005354:Fibrosarcoma / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism*; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001549:Benzamides; D016328:NF-kappa B; C505226:SM 7368; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9