Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling

✍ Scribed by Chi-Tai Yeh; Chi-Hao Wu; Gow-Chin Yen

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 499 KB
• Volume: 54
• Category: Article
• ISSN: 1613-4125
• DOI: 10.1002/mnfr.200900414

✦ Synopsis

Abstract

Metastasis is one of the most important factors related to breast cancer therapeutic efficacy. Ursolic acid, a naturally occurring triterpenoid, has various anticancer activities. In this study, we first observed that ursolic acid exerted a dose‐ and time‐dependent inhibitory effect on the migration and invasion of highly metastatic breast MDAMB231 cells at non‐cytotoxic concentrations. This effect was associated with reduced activities of metalloproteinase‐2 (MMP‐2) and u‐PA, which correlated with enhanced expression of tissue inhibitor of MMP‐2 and plasminogen activator inhibitor‐1, respectively. Ursolic acid suppressed the phosphorylation of Jun N‐terminal kinase, Akt and mammalian target of rapamycin, but had no effect on the phosphorylation of ERK and p38. Ursolic acid also strongly reduced the levels of NFκB p65, c‐Jun and c‐Fos proteins in the nucleus of MDAMB231 cells. A time‐dependent inhibition of the protein levels of Rho‐like GTPases, growth factor receptor‐bound protein 2, Ras and vascular endothelial growth factor in cytosol by ursolic acid treatment was also observed. In conclusion, we demonstrated that the anti‐invasive effects of ursolic acid on MDAMB231 cells might be through the inhibition of Jun N‐terminal kinase, Akt and mammalian target of rapamycin phosphorylation and a reduction of the level of NFκB protein in the nucleus, ultimately leading to downregulation of MMP‐2 and u‐PA expression. These results suggest that ursolic acid has potential as a chemopreventive agent for metastatic breast cancer.