Induction of apoptosis by the marine sponge (Mycale) metabolites, mycalamide A and pateamine
Induction of apoptosis by the marine sponge (Mycale) metabolites, mycalamide A and pateamine
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DOI：
10.1023/a:1011340827558
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发表时间：
2001-06-01
期刊：
影响因子：
7.2
通讯作者：
Miller, JH
中科院分区：
文献类型：
--
作者：
Hood, KA;West, LM;Miller, JH
海绵代谢物mycalamide A（myca-lamide）和pateamine具有极强的细胞毒性。虽然已显示霉酮酰胺抑制蛋白质合成，但这些化合物诱导细胞死亡的机制尚不清楚。使用DNA梯状排列、膜联蛋白V染色和形态学分析，我们证明这两种代谢产物在几种不同的细胞系中诱导细胞凋亡。此外，无论是与ras或bcr-abl癌基因转化后的32 D髓系细胞中的mycalamide和pateamine更有效的诱导细胞凋亡。在对蛋白质合成抑制剂放线菌酮和嘌呤霉素以及DNA损伤诱导剂胞嘧啶-β-D-阿拉伯呋喃糖苷（Ara-C）的反应中也观察到这种增加的敏感性。因此，我们建议，在32 D细胞中，Ras信号已被改变的致癌ras的组成性表达或Bcr/abl-mediated扰动的上游信号事件，增加的易感性凋亡的范围内的刺激被赋予。
The marine sponge metabolites mycalamide A (myca-lamide) and pateamine are extremely cytotoxic. While mycalamide has been shown to inhibit protein synthesis, the mechanism by which these compounds induce cell death is unknown. Using DNA laddering, Annexin-V staining, and morphological analysis, we demonstrate that both metabolites induce apoptosis in several different cell lines. Furthermore, both mycalamide and pateamine were more potent inducers of apoptosis in the 32D myeloid cell line after transformation with either the ras or bcr-abl oncogenes. This increased sensitivity was also observed in response to the protein synthesis inhibitors cycloheximide and puromycin, and cytosine-beta -D-arabinofurano-side (Ara-C), an inducer of DNA damage. We propose, therefore, that in 32D cells where Ras signalling has been altered either by constitutive expression of oncogenic ras or by Bcr/abl-mediated perturbation of upstream signalling events, increased susceptibility to apoptosis by a range of stimuli is conferred.