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

• Published in: Bioscience, biotechnology, and biochemistry Vol. 83; no. 9; pp. 1729 - 1739
• Main Authors: Hsu, Ming-Jie, Peng, Shu-Fen, Chueh, Fu-Shin, Tsai, Chang-Hai, Tsai, Fuu-Jen, Huang, Chih-Yang, Tang, Chih-Hsin, Yang, Jai-Sing, Hsu, Yuan-Man, Huang, Wen-Wen, Chung, Jing-Gung
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.09.2019; Oxford University Press
• Subjects: antineoplastic activity; beta catenin; cadherins; cell viability; fruits; gelatin; human cell lines; human diseases; human osteosarcoma U-2 OS cell; invasion; Lupeol; metastasis; migration; mitogen-activated protein kinase; natural foods; neoplasm cells; osteosarcoma; p38 MAPK signaling pathway; phosphatidylinositol 3-kinase; signal transduction; tau-protein kinase; tissue repair; migration; invasion; p38 MAPK signaling pathway; human osteosarcoma U-2 OS cell; Lupeol
• ISSN: 0916-8451; 1347-6947; 1347-6947
• DOI: 10.1080/09168451.2019.1606693

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