Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Eur J Pharmacol. 2010 Nov 10;646(1-3):1-11. doi: 10.1016/j.ejphar.2010.05.034. Epub 2010 Jun 12.
Multiple myeloma is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in multiple myeloma. Histone lysine methylation has emerged as a central epigenetic change in the organization of eukaryotic chromatin with far-reaching implications for the regulation of cell proliferation, cell-type differentiation, gene expression, genome stability, overall development, and genesis of cancer. Triptolide is the principal active ingredient in extracts from the Chinese herb Tripterygium wilfordii Hook.F (TwHF), and numerous studies have elucidated its antitumor property. Our experiments discovered that triptolide inhibited the proliferation of multiple myeloma cell line U266 in a time- and dose-dependent manner, induced G2/M cell cycle arrest and caspase-dependent apoptosis. Triptolide could decrease the expression of histone H3K4, H3K27 and H3K36 trimethylation in parallel with histone methyltransferases SMYD3, EZH2 and NSD1 respectively, which possibly was the anti-myeloma mechanism of triptolide.
多发性骨髓瘤是一种不可治愈的血液恶性肿瘤。不同的研究表明，多发性骨髓瘤中存在遗传和表观遗传改变。组蛋白赖氨酸甲基化已成为真核染色质组织的中心表观遗传变化，对细胞增殖、细胞类型分化、基因表达、基因组稳定性、整体发育和癌症发生有深远的影响。雷公藤红素是中药雷公藤（TwHF）提取物中的主要活性成分，大量研究已经阐明了其抗肿瘤特性。我们的实验发现，雷公藤红素能以时间和剂量依赖的方式抑制多发性骨髓瘤细胞系 U266 的增殖，诱导 G2/M 细胞周期阻滞和 caspase 依赖性细胞凋亡。雷公藤红素可分别降低组蛋白 H3K4、H3K27 和 H3K36 三甲基化的表达，同时降低组蛋白甲基转移酶 SMYD3、EZH2 和 NSD1 的表达，这可能是雷公藤红素的抗骨髓瘤机制。
