Oncotarget

Research Papers:

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

Xin-yuan Sun, Yue Qu, An-ran Ni, Gui-xiang Wang, Wei-bin Huang, Zhong-ping Chen, Zhu-fen Lv, Song Zhang, Holly Lindsay, Sibo Zhao, Xiao-nan Li and Bing-hong Feng _

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Oncotarget. 2017; 8:75232-75242. https://doi.org/10.18632/oncotarget.20744

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Abstract

Xin-Yuan Sun1, Yue Qu1,2, An-Ran Ni1, Gui-Xiang Wang1, Wei-Bin Huang1,4, Zhong-Ping Chen2, Zhu-Fen Lv3, Song Zhang1,5, Holly Lindsay6, Sibo Zhao6, Xiao-Nan Li6 and Bing-Hong Feng1

1Department of Pharmacology, College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China

2Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

3Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, China

4Department of Clinical Pharmacy, Puning People's Hospital, Puning, China

5Department of Pharmacy, The First People’s Hospital of Guangyuan, Guangyuan, China

6Preclinical Neuro-Oncology Research Program, Texas Children’s Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

Correspondence to:

Bing-Hong Feng, email: fengbh2010@163.com

Keywords: histone deacetylase inhibitor, N25, autophagy, glioma, HDAC3

Received: December 02, 2016     Accepted: August 06, 2017     Published: September 08, 2017

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 in vitro anti-proliferative effect and in vivo 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 in vitro and in vivo. 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.


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