The anticancer drug mithramycin A sensitises tumour cells to apoptosis induced by tumour necrosis factor (TNF).
The anticancer drug mithramycin A sensitises tumour cells to apoptosis induced by tumour necrosis factor (TNF).
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抗癌药毛霉素A A将肿瘤细胞对肿瘤坏死因子（TNF）诱导的凋亡敏感。
DOI：
10.1038/sj.bjc.6601824
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发表时间：
2004-05-17
影响因子：
8.8
通讯作者：
Murphy, FJ
中科院分区：
文献类型：
--
作者：
Duverger, V;Murphy, AM;Sheehan, D;England, K;Cotter, TG;Hayes, I;Murphy, FJ
在这篇报道中，我们发现米曲霉素在体外显着增加了肿瘤坏死因子对肿瘤细胞的直接细胞毒作用。广泛的caspase抑制剂zVAD-fmk可阻止对肿瘤坏死因子诱导的细胞凋亡的敏感性，而过表达bcl2则没有影响。米曲霉素还可增强Fas激动型抗体诱导的细胞死亡。相反，米曲霉素降低了因因子撤除而导致的细胞凋亡率。米曲霉素不影响肿瘤坏死因子诱导的核因子-κB(NF-KappaB)依赖性基因表达的激活。伴随着敏感性的增加，短剪接cFLIP变异体的蛋白水平下调。这些结果表明，米曲霉素以一种非依赖于NF-κB的方式促进肿瘤坏死因子诱导的细胞死亡，提示Fas相关死亡结构域蛋白在米特拉霉素的肿瘤坏死因子增敏作用中起着重要作用。
In this report we show that mithramycin considerably increases the direct cytotoxic effect of tumour necrosis factor (TNF) on tumour cells in vitro. Sensitisation to TNF-induced apoptosis was prevented by the broad caspase inhibitor zVAD-fmk, whereas overexpression of Bcl-2 had no effect. Mithramycin also potentiated cell death induced by Fas agonistic antibodies. In contrast, mithramycin reduced the percentage of cells undergoing apoptosis due to factor withdrawal. TNF-induced activation of NF-kappaB (NF-κB)-dependent gene expression was not modulated by mithramycin treatment. Concomitantly with the increased sensitivity, the protein level of the short-spliced cFLIP variant was downregulated. These results indicate that mithramycin enhances TNF-induced cell death in an NF-κB-independent manner, and suggest that the Fas-associated death domain protein plays a crucial role in the TNF-sensitising effect of mithramycin.
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影响因子：
3.8
作者：
Klampfer, L;Zhang, J;Nimer, SD
通讯作者：
Nimer, SD
影响因子：
64.5
作者：
Hsu, HL;Shu, HB;Goeddel, DV
通讯作者：
Goeddel, DV
DOI：
10.1073/pnas.84.12.4273
发表时间：
1987-06-01
影响因子：
11.1
作者：
KETTELHUT, IC;FIERS, W;GOLDBERG, AL
通讯作者：
GOLDBERG, AL
影响因子：
4.8
作者：
Kolonics, A;Apáti, A;Magócsi, M
通讯作者：
Magócsi, M
影响因子：
3.1
作者：
MILLER, DM;POLANSKY, DA;KOLLER, CA
通讯作者：
KOLLER, CA