Betulinic acid-induced apoptosis in leukemia cells
Betulinic acid-induced apoptosis in leukemia cells
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DOI：
10.1038/sj.leu.2403406
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发表时间：
2004-08-01
期刊：
影响因子：
11.4
通讯作者：
Jeremias, I
中科院分区：
文献类型：
--
作者：
Ehrhardt, H;Fulda, S;Jeremias, I
桦木酸（Betulinic acid，BA）是从桦树中提取的一种天然成分，在动物实验中能有效诱导神经外胚层和上皮肿瘤细胞的凋亡，且毒性很小。在这里，我们表明，BA诱导显着的凋亡，在65%的原发性小儿急性白血病细胞和所有白血病细胞系测试。当与常规使用的细胞毒性药物进行体外效率比较时，BA比10种标准疗法中的9种更有效，并且在肿瘤复发中特别有效。BA与任何细胞毒药物之间均未发现交叉耐药。白血病肿瘤细胞中的细胞内凋亡信号通路与神经外胚层细胞中发现的涉及半胱天冬酶而非死亡受体的通路相似。在离体线粒体中，BA诱导细胞色素c和Smac的释放。总之，BA有效地诱导白血病细胞凋亡，应进一步评估其作为未来治疗白血病的药物。
Betulinic acid (BA), a natural component isolated from Birch trees, effectively induces apoptosis in neuroectodermal and epithelial tumor cells and exerts little toxicity in animal trials. Here, we show that BA-induced marked apoptosis in 65% of primary pediatric acute leukemia cells and all leukemia cell lines tested. When compared for in vitro efficiency with conventionally used cytotoxic drugs, BA was more potent than nine out of 10 standard therapeutics and especially efficient in tumor relapse. No crossresistances were found between BA and any cytotoxic drug. Intracellular apoptosis signaling in leukemia tumor cells paralleled the pathway found in neuroectodermal cells involving caspases, but not death receptors. In isolated mitochondria, BA induced release of both cytochrome c and Smac. Taken together, BA potently induces apoptosis in leukemia cells and should be further evaluated as a future drug to treat leukemia.