Caffeoyl pyrrolidine derivative LY52 inhibits tumor invasion and metastasis via suppression of matrix metalloproteinase activity
- Anticancer Res. 2006 Sep-Oct;26(5A):3573-8.
- 1. School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
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.
Materials and 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.
Conclusion: LY52 might suppress invasion and metastasis of carcinoma cells via inhibition of MMP-2 and MMP-9 proteolytic activities.