Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells
Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells
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DOI：
10.1182/blood-2004-10-3915
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发表时间：
2005-04-15
期刊：
影响因子：
20.3
通讯作者：
Kawano, MM
中科院分区：
文献类型：
--
作者：
Ma, Z;Otsuyama, K;Kawano, MM
为寻找更有效的多发性骨髓瘤（MM）辅助治疗方法，我们研究了黄连解毒汤、桂枝茯苓丸和黄连汤对骨髓瘤细胞增殖和凋亡的影响。HLJDT抑制骨髓瘤细胞系的增殖和原代骨髓瘤细胞的存活，特别是MPC-1（-）未成熟骨髓瘤细胞，并通过降低线粒体膜电位和激活caspase-9和caspase-3，通过介导的途径诱导骨髓瘤细胞系的凋亡。进一步的实验证实HLJDT抑制骨髓瘤细胞增殖的作用是由黄芪引起的，且黄芪中的黄芩素与黄芩素或汉黄芩素相比，具有较强的生长抑制和诱导凋亡作用。黄芩素和黄芩苷抑制MPC-1未成熟骨髓瘤细胞的体外存活，而不是骨髓瘤患者的MPC-1（+）骨髓瘤细胞。黄芩素抑制IkB-α的磷酸化，随后降低IL-6和XIAP基因的表达以及caspase-9和caspase-3的活化。因此，HLJDT和黄芪对骨髓瘤细胞，尤其是MPC-1（-）未成熟骨髓瘤细胞具有抗增殖作用，黄芩素可能通过阻断IkB-α降解而发挥黄芪的抑制作用。
In the search for a more effective adjuvant therapy to treat multiple myeloma (MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Lian-Jie-Du-Tang (HLJDT), Gui-ZhiFu-Ling-Wan (GZFLW), and Huang-Lian-Tang (HLT) on the proliferation and apoptosis of myeloma cells. HLJDT inhibited the proliferation of myeloma cell lines and the survival of primary myeloma cells, especially MPC-1(-) immature myeloma cells, and induced apoptosis in myeloma cell lines via a mitochondria-mediated pathway by reducing mitochondrial membrane potential and activating caspase-9 and caspase-3. Further experiments confirmed that Scutellaria radix was responsible for the suppressive effect of HLJDT on myeloma cell proliferation, and the baicalein in Scutellaria radix showed strong growth inhibition and induction of apoptosis in comparison with balcalin or wogonin. Baicalein as well as baicalin suppressed the survival in vitro of MPC-1 immature myeloma cells rather than MPC-1(+) myeloma cells from myeloma patients. Baicalein inhibited the phosphorylation of IkB-alpha, which was followed by decreased expression of the IL-6 and XIAP genes and activation of caspase-9 and caspase-3. Therefore, HLJDT and Scutellaria radix have an anti proliferative effect on myeloma cells, especially MPC-1(-) immature myeloma cells, and baicalein may be responsible for the suppressive effect of Scutellaria radix by blocking IkB-alpha degradation.