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

Author:

Hsu Ming-Jie1,Peng Shu-Fen12,Chueh Fu-Shin3,Tsai Chang-Hai45,Tsai Fuu-Jen46,Huang Chih-Yang789,Tang Chih-Hsin91011,Yang Jai-Sing12,Hsu Yuan-Man1,Huang Wen-Wen1,Chung Jing-Gung19

Affiliation:

1. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan

2. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

3. Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan

4. China Medical University Children‘s Hospital, China Medical University, Taichung, Taiwan

5. Department of Healthcare Administration, Asia University, Taichung, Taiwan

6. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan

7. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

8. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan

9. Department of Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan

10. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan

11. Chinese Medicine Research Center, China Medical University, Taichung, Taiwan

12. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

Abstract

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.

Funder

China medical University

Medical Research Core Facilities Center, Office of Research & Development at China medical University

Publisher

Oxford University Press (OUP)

Subject

Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology

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