Effects of thymoquinone on isolated and cellular proteasomes
Effects of thymoquinone on isolated and cellular proteasomes
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DOI：
10.1111/j.1742-4658.2010.07629.x
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发表时间：
2010-05-01
期刊：
影响因子：
5.4
通讯作者：
Eleuteri, Anna Maria
中科院分区：
文献类型：
--
作者：
Cecarini, Valentina;Quassinti, Luana;Eleuteri, Anna Maria
百里醌是一种天然药物，具有抗氧化、抗增殖和促细胞凋亡的作用。在本研究中，我们探讨了百里醌对蛋白酶体复合物的影响，蛋白酶体复合物是去除受损、氧化和错误折叠蛋白质的主要系统。在纯化的20S复合物中，观察到亚基依赖性和组成依赖性的抑制，并且胰凝乳蛋白酶样和胰蛋白酶样活性对百里醌处理最敏感。用百里醌处理U87 MG和T98 G恶性胶质瘤细胞，测定20 S和26 S蛋白酶体活性。复合物的抑制在两种细胞系中是明显的，但主要是在U87 MG细胞中，并伴随着泛素缀合物的积累。在两种细胞系中均观察到p53和Bax（两种具有促凋亡活性的蛋白酶体底物）的积累。我们的研究结果表明，百里醌诱导选择性和时间依赖性的蛋白酶体抑制，无论是在分离的酶和胶质母细胞瘤细胞，并表明，这种机制可能与诱导癌细胞凋亡。
Thymoquinone, a naturally derived agent, has been shown to possess antioxidant, antiproliferative and proapoptotic activities. In the present study, we explored thymoquinone effects on the proteasomal complex, the major system involved in the removal of damaged, oxidized and misfolded proteins. In purified 20S complexes, subunit-dependent and composition-dependent inhibition was observed, and the chymotrypsin-like and trypsin-like activities were the most susceptible to thymoquinone treatment. U87 MG and T98G malignant glioma cells were treated with thymoquinone, and 20S and 26S proteasome activity was measured. Inhibition of the complex was evident in both cell lines, but predominantly in U87 MG cells, and was accompanied by accumulation of ubiquitin conjugates. Accumulation of p53 and Bax, two proteasome substrates with proapoptotic activity, was observed in both cell lines. Our results demonstrate that thymoquinone induces selective and time-dependent proteasome inhibition, both in isolated enzymes and in glioblastoma cells, and suggest that this mechanism could be implicated in the induction of apoptosis in cancer cells.