Caffeoyl pyrrolidine derivative LY52 inhibits tumor invasion and metastasis via suppression of matrix metalloproteinase activity.
BACKGROUND
LY52 is a caffeoyl pyrrolidine derivative designed to fit and extend into the active pocket of matrix metalloproteinase (MMP). In this study, the effects of LY52 on MMP-2 and MMP-9 activities and tumor invasion and metastasis were examined.


METHODS
MMP expression in SKOV3 cells was analyzed by gelatin zymography. The anti-invasion and anti-metastasis abilities of LY52 were evaluated with penetration of SKOV3 cells through Matrigel-coated membrane in vitro and pulmonary metastasis of Lewis lung carcinoma in mice, respectively.


RESULTS
LY52 significantly blocked the proteolytic activity of gelatinase. Gelatin zymography revealed that MMP-2 and MMP-9 expressions in SKOV3 cells were reduced in the presence of LY52. LY52 also suppressed SKOV3 cell invasion in vitro. Furthermore, a significant inhibition of pulmonary metastasis of Lewis lung carcinoma cells was observed in LY52-administrated mice.


CONCLUSIONS
LY52 might suppress invasion and metastasis of carcinoma cells via inhibition of MMP-2 and MMP-9 proteolytic activities.
Qu
Xianjun
X
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Yuan
Yunxia
Y
Xu
Wenfang
W
Chen
Minghui
M
Cui
Shuxiang
S
Meng
Hong
H
Li
Yan
Y
Makuuchi
Masatoshi
M
Nakata
Munehiro
M
Tang
Wei
W
D000818:Animals; D002109:Caffeic Acids / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary; D011509:Proteoglycans / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D002109:Caffeic Acids; D004338:Drug Combinations; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D011759:Pyrrolidines; C059485:matrigel; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C032519:pyrrolidine