Lupeol suppresses migration and invasion via p38/MAPK and PI3K/Akt signaling pathways in human osteosarcoma U-2 OS cells

Lupeol, one of the common components from the fruits and natural foods, has been reported to exert antitumor activities in many human cancer cell lines; however, its effects on osteosarcoma cell metastasis were not elucidated. In the present study, lupeol at 10-25 mu M induced cell morphological changes and decreased total viable cell number in U-2 OS cells. Lupeol (5-15 mu M) suppressed cell mobility, migration, and invasion by wound healing and transwell chamber assays, respectively. Lupeol inhibited the activities of MMP-2 and -9 in U-2 OS cells by gelatin zymography assay. Lupeol significantly decreased PI3K, pAKT, beta-catenin, and increased GSK3 beta. Furthermore, lupeol decreased the expressions of Ras, p-Raf-1, p-p38, and beta-catenin. Lupeol also decreased uPA, MMP-2, MMP-9, and N-cadherin but increased VE-cadherin in U-2 OS cells. Based on these observations, we suggest that lupeol can be used in anti-metastasis of human osteosarcoma cells in the future.