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

Biosci Biotechnol Biochem. 2019 Sep;83(9):1729-1739. doi: 10.1080/09168451.2019.1606693. Epub 2019 Apr 22.


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.

Keywords: Lupeol; human osteosarcoma U-2 OS cell; invasion; migration; p38 MAPK signaling pathway.

MeSH terms

  • Bone Neoplasms / enzymology
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neoplasm Invasiveness / prevention & control*
  • Neoplasm Metastasis / prevention & control*
  • Osteosarcoma / enzymology
  • Osteosarcoma / pathology*
  • Pentacyclic Triterpenes / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Pentacyclic Triterpenes
  • Phosphatidylinositol 3-Kinases
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinases
  • lupeol