A new proteasome inhibitor, TP-110, induces apoptosis in human prostate cancer PC-3 cells
A new proteasome inhibitor, TP-110, induces apoptosis in human prostate cancer PC-3 cells
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DOI：
10.1271/bbb.60697
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发表时间：
2007-04-01
影响因子：
1.6
通讯作者：
Ikeda, Daishiro
中科院分区：
文献类型：
--
作者：
Momose, Isao;Iijima, Masatomi;Ikeda, Daishiro
蛋白酶体抑制剂可用于治疗癌症。最近，我们发现了一个新的蛋白酶体抑制剂，TP-110，来自酪氨酸蛋白酶A产生的北里孢属。在这里，我们报告TP-110诱导人前列腺癌PC-3细胞凋亡。TP-110对PC-3细胞有较强的细胞毒性（IC_（50）= 0.05 μ m）。它增加了处于G（2）-M期的细胞数量，并增加了p21和p27蛋白的积累量，这是细胞周期进程的负调节因子。此外，它诱导PC-3细胞的凋亡沿着染色质凝聚和DNA片段化，TP-110诱导的凋亡似乎与caspase激活有关。TP-110不仅能抑制I-κ B的降解和核因子-κ B（NF-κ B B）的核转位，还能抑制NF-κ B B的DNA结合活性。这些结果表明TP-110在PC-3细胞中显示出强烈的生长抑制和凋亡。
Proteasome inhibitors are useful in the treatment of cancer. Recently, we found a new proteasome inhibitor, TP-110, derived from tyropeptin A produced by Kitasatospora sp. Here we report that TP-110 induces apoptosis in human prostate cancer PC-3 cells. TP-110 showed strong cytotoxicity to PC-3 cells (IC50 = 0.05 mu m). It increased the number of cells in the G(2)-M phase and increased the accumulated amounts of the p21 and p27 proteins, which are negative regulators of cell cycle progression. Furthermore, it induced apoptosis along with chromatin condensation and DNA fragmentation in PC-3 cells, and TP-110-induced apoptosis appeared to be associated with caspase activation. Additionally, TP-110 inhibited not only the degradation Of I kappa B and the nuclear translocation of nuclear factor-kappa B (NF-kappa B), but also the DNA binding activity of NF-kappa B. These results indicate that TP-110 shows a strong growth inhibition and apoptosis in PC-3 cells.