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新型组蛋白去乙酰化酶抑制剂N25通过抑制HDAC3发挥抗肿瘤作用并诱导人胶质瘤细胞自噬。

Novel histone deacetylase inhibitor N25 exerts anti-tumor effects and induces autophagy in human glioma cells by inhibiting HDAC3.

作者信息

Sun Xin-Yuan, Qu Yue, Ni An-Ran, Wang Gui-Xiang, Huang Wei-Bin, Chen Zhong-Ping, Lv Zhu-Fen, Zhang Song, Lindsay Holly, Zhao Sibo, Li Xiao-Nan, Feng Bing-Hong

机构信息

Department of Pharmacology, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Oncotarget. 2017 Sep 8;8(43):75232-75242. doi: 10.18632/oncotarget.20744. eCollection 2017 Sep 26.

DOI:10.18632/oncotarget.20744
PMID:29088860
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5650415/
Abstract

N25, a novel histone deacetylase inhibitor, was created through structural modification of suberoylanilide hydroxamic acid. To evaluate the anti-tumor activity of N25 and clarify its molecular mechanism of inducing autophagy in glioma cells, we investigated its anti-proliferative effect and anticancer effect. Moreover, we detected whether N25 induces autophagy in glioma cells by transmission electron microscope and analyzed the protein expression level of HDAC3, Tip60, LC3 in glioma samples by western blot. We additionally analyzed the protein expression level of HDAC3, Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment with N25 in glioma cells. Our results showed that the anti-tumor activity of N25 in glioma cells is slightly stronger than SAHA both i and . We found that N25 induced autophagy, and HDAC3 was significantly elevated and Tip60 and LC3 significantly decreased in glioma samples compared with normal brain tissues. Nevertheless, N25 inhibited HDAC3 and up-regulated the protein expression of Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment of glioma cells with N25. In conclusion, these data suggest that N25 has striking anti-tumor activity in part due to inhibition of HDAC3. Additionally, N25 may induce autophagy through inhibiting HDAC3.

摘要

新型组蛋白去乙酰化酶抑制剂N25是通过对辛二酰苯胺异羟肟酸进行结构修饰而合成的。为了评估N25的抗肿瘤活性并阐明其在胶质瘤细胞中诱导自噬的分子机制，我们研究了其抗增殖作用和抗癌效果。此外，我们通过透射电子显微镜检测N25是否能在胶质瘤细胞中诱导自噬，并通过蛋白质免疫印迹法分析胶质瘤样本中HDAC3、Tip60、LC3的蛋白表达水平。我们还分析了用N25处理胶质瘤细胞后HDAC3、Tip60、ULK1（自噬相关基因1）和Beclin-1（自噬相关基因6）的蛋白表达水平。我们的结果表明，N25在胶质瘤细胞中的抗肿瘤活性略强于伏立诺他。我们发现，与正常脑组织相比，N25在胶质瘤样本中诱导自噬，且HDAC3显著升高，Tip60和LC3显著降低。然而，用N25处理胶质瘤细胞后，N25抑制HDAC3并上调Tip60、ULK1（自噬相关基因1）和Beclin-1（自噬相关基因6）的蛋白表达。总之，这些数据表明，N25具有显著的抗肿瘤活性，部分原因是其对HDAC3的抑制作用。此外，N25可能通过抑制HDAC3诱导自噬。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/184fa66bdfb2/oncotarget-08-75232-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/df954d9311c9/oncotarget-08-75232-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/31dd19c3f9d5/oncotarget-08-75232-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/42655d611fb4/oncotarget-08-75232-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/184fa66bdfb2/oncotarget-08-75232-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/df954d9311c9/oncotarget-08-75232-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/31dd19c3f9d5/oncotarget-08-75232-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/42655d611fb4/oncotarget-08-75232-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce4/5650415/184fa66bdfb2/oncotarget-08-75232-g004.jpg

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