Studies on the Mechanisms of Cancer Chemoprevention by Flavonoids from Propolis and Tea

• Main Authors: Meng-Shih Weng, 翁孟仕
• Other Authors: Jen-Kun Lin
• Format: Others
• Language: en_US
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/08880065096355087531

博士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 95 === Chemoprevention of cancer aims to prevent, arrest, or reverse either the initiation phase of carcinogenesis or the progression of neoplastic cells to cancer. A large number of natural and synthetic compounds have cancer preventive properties in cell culture or animal model studies. Several specific plant phenolic compounds, especially flavonoids, were reported to inhibit mutagenesis and carcinogenesis. Flavonoids have shown many biological properties, including inhibit the cell cycle, cell proliferation, and oxidative stress, and to induce apoptosis that may account for cancer chemoprevention. In this dissertation, we investigate the cancer chemoprevention of some flavonoids from propolis and tea. We hope our studies could provide a new direction to investigate new chemopreventive compounds for cancer control. Propolis has been reported to exert a widely spectrum of biological functions, including anticancer and antioxidant activities. However, the molecular mechanisms of the anti-cancer properities of propolis components have not been completely understood. In our study, we investigate the molecular mechanism of chrysin (5, 7-dihydroxyflavone) and a novel component namely propolin H on cell cycle regulation. Our data indicated that chrysin and propolin H blocked rat C6 glioma and H460 lung carcinoma cell line cell cycle progression at the G1 phase, respectively. Both cyclin-dependent kinase 2 (CDK2) and 4 (CDK4) kinase activities were down-regulated by chrysin and propolin H, and the expression of cyclin-dependent kinase inhibitor, p21Waf1/Cip1, to be significantly increased in chrysin-and propolin H-treated C6 glioma and H460 lung carcinoma cells, respectively. The content of the p21Waf1/Cip1 protein was increased in correlated with the elevation in p53 levels in propolin H-treated H460 cells but not in chrysin-treated C6 glioma cells. We also showed that chrysin induced p38-MAPK activation, and inhibition of p38-MAPK attenuated chrysin-induced p21Waf1/Cip1 expression. In propolin H-treated cells, propolin H also enhanced the expression of p21Waf1/Cip1 in p53-mutant and p53-null lung carcinoma cell lines following the induction of G1 arrest and apoptosis. These results suggest that chrysin and propolin H exerts its growth-inhibitory effects through activation of p21Waf1/Cip1 protein and then inhibition of CDKs kinase activities followed by blockade cell cycle progression. Obesity is a growing problem in many countries worldwide and is associated with many health risks such as cancer. Tea catechins have been reported to possess various biological and pharmacological effects, such as anti-oxidation, anti-carcinogenic and anti-atherogenic activities, but little information is available about the effects of tea catechins on lipid metabolism and body fat accumulation. In our study, we investigate the hypolipidemic effect of oolong, black, pu-erh, and green tea leaves in male Sprague-Dawley rats. In lowering body weight and serum triglyceride levels, oolong and pu-erh tea leaves seem to have stronger effect than green tea leaves. However, in lowering the level of total cholesterol, pu-erh and green tea were more efficient than oolong and black tea. Furthermore, the level of LDL-C was significant decrease in feeding all of teas. These results indicated that the fully-fermented pu-erh and black tea leaves and partially-fermented oolong tea leaves were more effective on their hypolipidemic effects as compared to the non-fermented green tea leaves. To further investigate the mechanism of tea polyphenols on lipid metabolism. We investigated the effects of black tea polyphenol, theanaphthoquinone (TNQ) on the expression of Fatty acid synthase in human breast cancer cells. Fatty acid synthase (FAS) is an important enzyme participating in lipid metabolism and is related to various human diseases including obesity, cardiovascular disease and cancer. In this study, TNQ was found to suppress EGF-induced FAS mRNA and protein expressions and nuclear translocation of SREBP-1 in MDA-MB-231 cells. This suppression was through down-regulation of PI 3-kinase/Akt sinaling. Furthermore, suppression of EGFR or ErbB-2 activation resulted in down-regulation of EGF-induced FAS expression. Our data also indicated that TNQ inhibited constitutive FAS expression and induced cell death in ErbB-2-overexpressed cells. Finally, our study indicated that flavonoids from propolis and tea could serve as a candidate to become chemopreventive agent