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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vine'.
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Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vine'.

机译：从中草药“雷神藤”提取的雷公藤甲素抑制肿瘤细胞蛋白酶体的活性。

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AIMS: The molecular mechanisms of triptolide responsible for its antitumor properties are not yet fully understood. The ubiquitin/proteasome system is an important pathway of protein degradation in cells. This study investigated whether triptolide may inhibit proteasomal activity and induce apoptosis in human cancer cells. MATERIALS AND METHODS: In vitro proteasome inhibition was measured by incubation of a purified 20S proteasome with triptolide. Human breast and prostate cancer cell lines were also treated with different doses of triptolide for different times, followed by measurement of proteasome inhibition (levels of the chymotrypsin-like activity, ubiquitinated proteins and three well-known proteasome target proteins, p27, IkappaB-alpha and Bax) and apoptosis induction (caspase-3 activity and PARP cleavage). RESULTS: Triptolide did not inhibit the chymotrypsin-like activity of purified 20S proteasome. However, treatment of triptolide was able to cause decreased levels of cellular proteasomal chymotrypsin-like activity and accumulation of ubiquitinated proteins and three well-known proteasome target proteins in human breast and prostate cancer cells, associated with apoptosis induction. CONCLUSION: It is possible that at least one of metabolites of triptolide has proteasome-inhibitory activity.
机译：目的：雷公藤内酯醇的抗肿瘤特性的分子机制尚未完全了解。泛素/蛋白酶体系统是细胞中蛋白质降解的重要途径。这项研究调查了雷公藤甲素是否可以抑制蛋白酶体活性并诱导人癌细胞凋亡。材料与方法：通过将纯化的20S蛋白酶体与雷公藤甲素一起孵育来测量体外蛋白酶体的抑制作用。还使用不同剂量的雷公藤内酯醇在不同时间处理人乳腺癌和前列腺癌细胞系，然后测量蛋白酶体抑制作用（胰凝乳蛋白酶样活性，泛素化蛋白和三种众所周知的蛋白酶体靶标蛋白p27，IkappaB-alpha的水平和Bax）和凋亡诱导（caspase-3活性和PARP裂解）。结果：雷公藤甲素未抑制纯化的20S蛋白酶体的胰凝乳蛋白酶样活性。然而，雷公藤甲内酯的治疗能够引起细胞蛋白酶体胰凝乳蛋白酶样活性水平降低以及遍在蛋白化的蛋白质和三种众所周知的蛋白酶体靶标蛋白质在人乳腺癌和前列腺癌细胞中的积累，与凋亡诱导有关。结论：雷公藤内酯醇的至少一种代谢物可能具有蛋白酶体抑制活性。

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