Penta-acetyl geniposide inhibits cell cycle and phosphoinositide 3-kinase signaling pathway

• Main Authors: Yun-Jing Chang, 張雲菁
• Other Authors: Chau - Jong Wang, Ph. D.
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/98562587791323657934

碩士 === 中山醫學院 === 生物化學研究所 === 89 === Penta-acetyl geniposide [(Ac)5GP] was a acetylated product from geniposide, a glycoside existing in Gardenia fructus. In recent years, many studies indicated that anticarcinogenic drugs inhibiting the proliferation and malignancy of cancer cell could be via inducing cancer cell apoptosis or changing cell cycle progression. In our previous researches, we had explored that (Ac)5GP can inhibit C-6 glioma cell growth and induce apoptosis. We further designed a series of experiments to clarify the mechanisms existing in the anticarcinogenic effect of (Ac)5GP. In this study, we found that (Ac)5GP can arrest C-6 glioma cell cycle at G1 phase. After treated with (Ac)5GP for 0, 2, 4, 6, 8, 24 h, the expression of p53 protein was increased gradually and the expression of p21 was induced significantly. Furthermore, the treatment of (Ac)5GP also inhibited the expression of phospho-Rb. Because of above, we issued that (Ac)5GP maybe inhibited the expressions of p53, p21, cyclin D1 and phospho-Rb to arrest cell cycle at G0/G1 phase. At this moment, the expression of CDK4 was increased. On the other hand, after treated (Ac)5GP for 4 h, the expressions of phosphoinositide 3-kinase （PI3-K）, phospho-Akt and phospho-Bad were reduced but the expression of phospho-GSK-3-b was significant induced. Taken the above together, the pathway in (Ac)5GP inducing cell apoptosis could be via the inhibition of PI3-K pathway. We also detected the MAPK pathway including the expressions of p38, phospho-p38, phospho-JNK. (Ac)5GP did not affect the MAPK pathway. Conclusively, we suggested that (Ac)5GP can arrest the cell cycle at G1 phase through activating p53 pathway; and (Ac)5GP can induce cell apoptosis via inhibiting PI3-K pathway.