组蛋白去乙酰化酶抑制剂depsipeptide通过FoxO1-Bim 通路来诱导细胞的凋亡

Histone deacetylase (HDAC) inhibitors have been shown to induce cell cycle arrest and apoptosis in cancer cells. However, the mechanisms of HDAC inhibitor induced apoptosis are not completely understood. In this study, a novel HDAC inhibitor, depsipeptide was found to induce p53-independent apoptosis in human lung cancer cells. Further study showed that Bim, a BH3-only pro-apoptotic protein, was significantly up-regulated by depsipeptide in cancer cells, indicating Bim may play a role in this depsipeptide induced apoptosis. In additional experiments, Bim’s function in depsipeptide-induced apoptosis was confirmed by knock down of Bim with RNAi. Furthermore, depsipeptide-induced expression of Bim was found to be dependent on forkhead transcription factor 1 (FoxO1) by FoxO1 siRNA. These data show for the first time that HDAC inhibitor may induce apoptosis through the FoxO1-Bim pathway.