Tangeretin derivative inhibits cell growth in human prostate cancer cells

• Main Authors: Chen, Yin-Bo, 陳胤伯
• Other Authors: Chen, Yu-Kuo
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/89556735910011076209

碩士 === 國立屏東科技大學 === 食品科學系所 === 104 === Tangeretin (TAN), a kind of polymethoxyflavones (PMFs) widely found in citrus peels, has been proved to have many kinds of bioactivities including anti-inflammatory, antioxidant and antitumor activities. Studies reported that the 5-demethyltangeretin (5-DTAN), hydoxylated derivative of TAN, had significant inhibitory effect on several kinds of cancer cells, which is much better than those of TAN. However the low solubility of 5-DTAN in water and edible oil limits its availability and accessibility in biological system. The purpose of this study is to prepare 5-acetyl-6,7,8,4'-tetramethylnortangeretin (5-ATAN) for improving its availability, and to investigate the inhibitory effect of 5-ATAN and 5-DTAN on cell growth in human prostate cancer PC-3 cells. The results showed that 5-ATAN and 5-DTAN can both effectively inhibit the cell viability in PC-3 cells and in a dose-dependent manner. When treated the cells with 20 µM, 5-ATAN shows the better inhibitory activity. It means that modification of 5-DTAN into 5-ATAN not only improves its solubility but also the inhibitory effect in cancer cells. Moreover, treatment of 5-ATAN and 5-DTAN increased the sub-G1 phase population in PC-3 cells. 5-ATAN can also induced G2/M arrest in PC-3 cells. It shows tangeretin derivative can inhibit the prostate cancer cell growth by inducing cell cycle arrest and leading to apoptosis. In Intracellular level experiments, the results showed that the good solubility of the 5-ATAN, the sample not only can be effectively into the cell, but also to achieve the effect of suppressing the growth of cancer cells. In cell metastasis test, 5-ATAN decreased the cell migration dose dependently and decrease the activity of MMP-2 and MMP-9. In western blotting, 5-ATAN control the expression of apoptosis related Bax and bcl-xL, and inhibit the expression of cell cycle G2/M phase related protein cdc25c, cdc2 and cyclin B1. In animal study, 5-DTAN and 5-ATAN can both inhibit the tumor growth. 5-ATAN shows higher inhibitory effect on tumor growth than those of 5-DTAN group. Overall, in PC-3 cells we infer the mechanism of 5-ATAN in cell growth inhibition in human prostate cancer cells may due to induction of the cell cycle arrest and apoptosis and inhibition of metastasis, and has the potential for preventing prostate cancer.