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

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Lupeol, a triterpenoid found in fruits and natural foods, exhibits known antitumor properties.
• The anti-metastatic effects of lupeol on osteosarcoma cells remain largely uninvestigated.

Purpose of the Study:

• To investigate the effects of lupeol on the metastasis of human osteosarcoma cells (U-2 OS).
• To elucidate the molecular mechanisms underlying lupeol's potential anti-metastatic activity in osteosarcoma.

Main Methods:

• Cell viability and morphological changes were assessed.
• Cell mobility, migration, and invasion were evaluated using wound healing and Transwell assays.
• Enzyme activities (MMP-2, MMP-9) were measured via gelatin zymography.
• Western blotting was used to analyze the expression of key signaling proteins (PI3K, AKT, GSK3β, β-catenin, Ras, Raf-1, p38, uPA, cadherins).

Main Results:

• Lupeol treatment reduced U-2 OS cell viability and induced morphological changes.
• Lupeol significantly suppressed cell migration and invasion.
• Inhibition of matrix metalloproteinases (MMP-2, MMP-9) and urokinase plasminogen activator (uPA) was observed.
• Lupeol modulated signaling pathways including PI3K/AKT, Wnt/β-catenin, and MAPK, affecting proteins like β-catenin, GSK3β, Ras, p-Raf-1, and p-p38.
• Expression of N-cadherin was decreased, while VE-cadherin was increased by lupeol.

Conclusions:

• Lupeol demonstrates significant anti-metastatic potential against human osteosarcoma cells.
• The anti-metastatic effects are mediated through the modulation of key signaling pathways and proteins involved in cell invasion and migration.
• Lupeol warrants further investigation as a potential therapeutic agent for preventing osteosarcoma metastasis.