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

ABSTRACT

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 μM induced cell morphological changes and decreased total viable cell number in U-2 OS cells. Lupeol (5–15 μM) 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, β-catenin, and increased GSK3β. Furthermore, lupeol decreased the expressions of Ras, p-Raf-1, p-p38, and β-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.

Graphical Abstract

The possible signaling pathways for lupeol suppressed cell migration and invasion in U-2 OS cells in vitro

KEYWORDS:

• Lupeol
• human osteosarcoma U-2 OS cell
• migration
• invasion
• p38 MAPK signaling pathway

Author contributions

Study conception and design: M.J.H., W.W.H., and J.G.C.; Acquisition of data: M.J.H., S.F.P. and F.S.C.; Analysis and interpretation of data: F.J.T., C.Y.H., C.H.T., J.S.Y., and Y.M.H.; Drafting of manuscript: S.F.P., W.W.H., and J.G.C.; Critical revision: W.W.H. and J.G.C. All authors discussed the results and commented on the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The present study was supported by grants CMU106-ASIA-01 from China Medical University, Taichung, Taiwan, R.O.C. Experiments and data analysis were performed in part through the use of the Medical Research Core Facilities Center, Office of Research & Development at China Medical University, Taichung, Taiwan.