title: Using caffeoyl pyrrolidine derivative LY52, a potential inhibitor of matrix metalloproteinase-2, to suppress tumor invasion and metastasis.
abstract: LY52 is a caffeoyl pyrrolidine derivative designed to fit the S'1 active pocket of gelatinases that act in tumor invasion and metastasis. Herein, we examined the effects of LY52 on expression of matrix metalloproteinase (MMP)-2 expression in human breast cancer MDA-MB-231 cells and on in vitro invasion and in vivo metastasis. LY52 significantly blocked MMP-2 activity as evidenced by a decrease in the degradation of succinylated gelatin. Gelatin zymography analysis showed that LY52 (0.1-200 microg/ml) inhibited expression of active MMP-2 in concanavalin A-stimulated MDA-MB-231 cells. Inhibition of MMP-2 expression was also observed in tissue of tumor xenografts in mice that were orally administered LY52 (25 or 100 mg/kg). Furthermore, LY52 displayed an inhibitory effect on in vitro invasion of MDA-MB-231 cells and pulmonary metastasis of B16F10 murine melanoma cells in mice without significant toxic effects. These results suggest that LY52 is a potential MMP-2 inhibitor that may effectively suppress tumor invasion and metastasis.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Shandong, P.R. China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Qu
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Yuan
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Tian
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Xu
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Shu-Xiang
authors.initials: SX
authors.lastname: Cui
authors.forename: Qian
authors.initials: Q
authors.lastname: Guo
authors.forename: Ruoyan
authors.initials: R
authors.lastname: Gai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
authors.forename: Munehiro
authors.initials: M
authors.lastname: Nakata
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D002109:Caffeic Acids; C515003:LY52 compound; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011392:Proline; D020778:Matrix Metalloproteinase 2