Galloyl cyclic-imide derivative CH1104I inhibits tumor invasion through suppressing matrix metalloproteinase activity

• DOI: 10.1097/cad.0b013e328313e15b
• Publication Date: 2010-01-27T06:31:58Z
• Authors: Ming-Hui Chen; Shu-Xiang Cui; Yan-Na Cheng; Li-Rui Sun; Qian-Bin Li; Wen-Fang Xu; Stephen G. Ward; Wei Tang; Xian-Jun Qu
• Keywords: Lewis lung carcinoma; Matrix metalloproteinase inhibitor; Zymography; Type IV collagen; MMP2; Gelatinase A

Matrix metalloproteinase (MMP)-2 and MMP-9 have been associated with the ability of tumor cells to metastasize because their capacity degrade type IV collagen, main component basement membrane, elevated expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-((S)-2,6-dioxo-3-(3,4,5-trimethoxybenzamido) piperidin-1-yl) acetamido) hexanoate (CH1104I) is a galloyl cyclic-imide derivative designed fit extend into S1′ active pocket MMP-2 MMP-9. We aimed evaluate efficacy CH1104I as candidate compound for antiinvasion antimetastasis cells. significantly blocked gelatinase activity evidenced by decrease degradation succinylated gelatin. Gelatin zymography analysis showed that (7–210 μmol/l) inhibited produced human ovarian carcinoma SKOV3 Inhibition was also observed using assays immunocytochemical staining western blot analysis. The results suppressed zymogens effects on invasion migration were then measured. Both trans-well motility assay wound scratch indicated very effective antimigration Furthermore, Lewis lung model used vivo. A significant inhibition pulmonary metastasis CH1104I-administrated mice (25–100 mg/kg). These suggest potential inhibitor may effectively suppress metastasis.