Inhibitory Effect of Flavonoids on 26S Proteasome Activity

被引:27
|
作者
Chang, Tsui-Ling [1 ]
机构
[1] Natl Univ Tainan, Dept Biol Sci & Technol, Tainan, Taiwan
关键词
5,6,3 ',4 '-Tetrahydroxy-7-methoxyflavone; MG132; 26S proteasome; flavonoids; 5,6,4 '-trihydroxy-7,3 '-dimethoxyflavone; proteasome inhibitor; ubiquitin; HUMAN CANCER-CELLS; DIETARY FLAVONOIDS; POLYUBIQUITIN; DEGRADATION; BORTEZOMIB; PROTEIN; ATP;
D O I
10.1021/jf9017492
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Inhibiting proteasomal degradation has been shown to induce apoptosis in tumor cells. Utilization of proteasome inhibition is therefore one approach to anticancer therapy. Some of the flavonoids can induce cell apoptosis via inhibiting proteasome 26S activity. In this study, the inhibition of 26S proteasome from pig red blood cells was analyzed on 12 flavones, 5 flavanones, and 9 isoflavones by using a proteolysis assay. Several flavonoids such as apigenin-6-hydroxy-7-O-beta-D-glucoside, quercetin, rutin, 6-hydroxyapigenin, 5,6,4'-trihydroxy-7,3'-dimethoxyflavone, 5,6,3',4'-tetrahydroxy-7-methoxyflavone, glycitecin, and 6,7,4'-trihydroxyisoflavone inhibited the chymotrypsin-like, caspase-like, or trypsin-like activity of 26S proteasome when Suc-LLVY-AMC, Z-LLE-AMC, and Ac-RLR-AMC were used as substrates. Three peptidase activities of flavonoids were found to be significantly correlated with one another. Flavones had significantly stronger inhibitory effects on chymotrypsin-like and caspase-like activities than flavanones and isoflavones. 5,6,3',4'-Tetrahydroxy-7-methoxyflavone, 5,6,4'-trihydroxy-7,3'-dimethoxyflavone, and quercetin displayed a mixed type inhibition of 26S by Lineweaver-Burk plots analysis. Furthermore, 5,6,3',4'-tetrahydroxy-7-methoxyflavone is found to have a higher inhibitory effect on 26S proteasome activities and is the only flavonoid to inhibit all three peptidase activities, whereas the inhibition of flavonoids was not affected by ubiquitin-induced stimulation of the three peptidase activities of 26S proteasome; 5,6,3,4'-tetrahydroxy-7-methoxyflavone inhibited 75% casein degradation. These results suggest that both the 6-hydroxy and 7-methoxy positions of the flavone may play an important role in targeting 26S activity.
引用
收藏
页码:9706 / 9715
页数:10
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