Molecular mechanism of matrine-induced apoptosis in leukemia K562 cells
Molecular mechanism of matrine-induced apoptosis in leukemia K562 cells
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DOI：
10.1142/s0192415x06004557
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发表时间：
2006-01-01
影响因子：
5.7
通讯作者：
Jiang, Jikai
中科院分区：
文献类型：
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作者：
Liu, Xiao-Shan;Jiang, Jikai
苦参碱是从中药苦参中提取的一种低毒生物碱，可诱导白血病K562细胞凋亡。在这项研究中，这种凋亡事件的机制进行了调查。苦参碱处理K562细胞比处理非癌成纤维细胞NIH 3 T3细胞更显著地抑制细胞存活。当苦参碱浓度高于0.2mg/ml时，K562细胞凋亡率增加，多聚腺苷二磷酸核糖聚合酶（PARP）和半胱天冬酶-3（caspase-3）的裂解呈剂量依赖性。caspase-3抑制剂（z-DEVD-festival）或caspase-3抑制剂（z-VAD-festival）几乎完全抑制苦参碱诱导的细胞凋亡。此外，苦参碱还可增加促凋亡蛋白bax的表达，并引起细胞色素C的释放。两者合计，结果表明，苦参碱诱导细胞色素C介导的，半胱天冬酶依赖的细胞凋亡。
Matrine, a low toxic alkaloid purified from the Chinese herb Kushen, has been reported to induce apoptosis in leukemia K562 cells. In this study, the mechanism underling this apoptotic event was investigated. Treatment of K562 cells with matrine resulted in inhibition of cell survival more significantly than treatment of non-cancer fibroblast NIH3T3 cells. When K562 cells were incubated with matrine in higher than 0.2 mg/ml doses for 48 hours, the apoptotic cells were increased and both poly (ADP-ribose) polymerase (PARP) and caspase-3 were cleaved in a dose dependent manner. General caspase inhibitor (z-VAD-fmk) or caspase-3 inhibitor (z-DEVD-fmk) almost completely suppressed matrine-induced apoptosis. In addition, matrine increased proapoptotic protein bax and caused the release of cytochrome C. Taken together, the results suggest that matrine induces a cytochrome C-mediated, caspase-dependent apoptosis.