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
a Department of Biological Science and Technology, China Medical University , Taichung , Taiwan.
b Department of Medical Research, China Medical University Hospital , Taichung , Taiwan.
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.
羽扇豆醇是水果和天然食物中的常见成分之一，据报道它在多种人类癌细胞系中具有抗肿瘤活性；然而，其对骨肉瘤细胞转移的影响尚未阐明。在本研究中，10 - 25 μM的羽扇豆醇可诱导U - 2 OS细胞发生形态变化并减少总活细胞数。羽扇豆醇（5 - 15 μM）分别通过伤口愈合实验和Transwell小室实验抑制细胞的移动、迁移和侵袭。通过明胶酶谱分析，羽扇豆醇可抑制U - 2 OS细胞中MMP - 2和MMP - 9的活性。羽扇豆醇可显著降低PI3K、pAKT、β - 连环蛋白水平，并增加GSK3β的水平。此外，羽扇豆醇可降低Ras、p - Raf - 1、p - p38和β - 连环蛋白的表达。羽扇豆醇还可降低U - 2 OS细胞中uPA、MMP - 2、MMP - 9和N - 钙黏蛋白的水平，但增加VE - 钙黏蛋白的水平。基于这些观察结果，我们认为羽扇豆醇未来可用于人类骨肉瘤细胞的抗转移治疗。
