Myrtucommulone from Myrtus communis induces apoptosis in cancer cells via the mitochondrial pathway involving caspase-9
Myrtucommulone from Myrtus communis induces apoptosis in cancer cells via the mitochondrial pathway involving caspase-9
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DOI：
10.1007/s10495-007-0150-0
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发表时间：
2008-01-01
期刊：
影响因子：
7.2
通讯作者：
Werz, Oliver
中科院分区：
文献类型：
--
作者：
Tretiakova, Irina;Blaesius, Dagmar;Werz, Oliver
Myrtucommulone (MC) 是一种独特的非异戊二烯化酰基间苯三酚，包含在桃金娘 (Myrtus communis) 的叶子中。在这里，我们探讨了 MC 诱导癌细胞凋亡的潜力。 MC 有效诱导不同癌细胞系的细胞死亡 (EC50 3-8 μM)，具有细胞凋亡的特征，通过 caspase-3、-8 和 -9 的激活、聚（ADP-核糖）聚合酶 (PARP) 的裂解、核小体释放到细胞质中以及 DNA 断裂来观察。 MC 对未转化的人外周血单核细胞 (PBMC) 或包皮成纤维细胞的细胞毒性要小得多（EC50 细胞死亡 = 20-50 μM），高达 30 μM 的 MC 几乎不会引起人 PBMC 中 PARP、caspase-3、-8 和 -9 的加工。 MC 诱导的细胞凋亡是由内在而非外在死亡途径介导的。因此，MC 导致 MM6 细胞线粒体膜电位丧失，并引起线粒体释放细胞色素 c。有趣的是，缺乏 caspase-9 的 Jurkat 细胞能够抵抗 MC 诱导的细胞死亡，并且没有明显的 PARP 或 caspase-8 加工。在缺乏 CD95 (Fas、APO-1) 信号传导、FADD 或 caspase-8 的细胞系中，MC 仍然能够有效诱导细胞死亡和 PARP 裂解。总之，MC 通过线粒体细胞色素 c/Apaf-1/caspase-9 途径诱导癌细胞系凋亡，对非转化细胞具有边缘细胞毒性。
Myrtucommulone (MC) is a unique, nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis). Here, we addressed the potential of MC to induce apoptosis of cancer cells. MC potently induced cell death of different cancer cell lines (EC50 3-8 mu M) with characteristics of apoptosis, visualized by the activation of caspase-3, -8 and -9, cleavage of poly(ADP-ribose)polymerase (PARP), release of nucleosomes into the cytosol, and DNA fragmentation. MC was much less cytotoxic for non-transformed human peripheral blood mononuclear cells (PBMC) or foreskin fibroblasts (EC50 cell death = 20-50 mu M), and MC up to 30 mu M hardly caused processing of PARP, caspase-3, -8 and -9 in human PBMC. MC-induced apoptosis was mediated by the intrinsic rather than the extrinsic death pathway. Thus, MC caused loss of the mitochondrial membrane potential in MM6 cells and evoked release of cytochrome c from mitochondria. Interestingly, Jurkat cells deficient in caspase-9 were resistant to MC-induced cell death and no processing of PARP or caspase-8 was evident. In cell lines deficient in either CD95 (Fas, APO-1) signalling, FADD or caspase-8, MC was still able to potently induce cell death and PARP cleavage. Conclusively, MC induces apoptosis in cancer cell lines, with marginal cytotoxicity for non-transformed cells, via the mitochondrial cytochrome c/Apaf-1/caspase-9 pathway.