Antitumor effects of a novel histone deacetylase inhibitor NK-HDAC-1 on breast cancer

Li,Zhong-Hua; Zhang,Xiao-Bing; Han,Xi-Qian; Feng,Cong-Ran; Wang,Feng‑Shan; Wang,Peng  George; Shen,Jie; Shi,Yi-Kang

doi:10.3892/or.2013.2434

Antitumor effects of a novel histone deacetylase inhibitor NK-HDAC-1 on breast cancer

Authors:
- Zhong-Hua Li
- Xiao-Bing Zhang
- Xi-Qian Han
- Cong-Ran Feng
- Feng‑Shan Wang
- Peng George Wang
- Jie Shen
- Yi-Kang Shi
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Affiliations: National Glycoengineering Research Center and School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China, School of Pharmacy, Nankai University, Tianjin 300071, P.R. China
Published online on: April 29, 2013 https://doi.org/10.3892/or.2013.2434
Pages: 499-505

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Abstract

Histone deacetylases (HDACs) are overexpressed in various types of primary human cancer and have become attractive targets for cancer therapy. We designed and synthesized a series of new class of HDAC inhibitors (HDACi). Among these, S-(E)-3-(1-(1-(benzo[d]oxazol-2-yl)-2-methylpropyl)-1H-1,2,3-triazol-4-yl)-N-hydroxyacrylamide (NK-HDAC-1) showed potent antitumor activity. In the present study, we examined the antitumor effects of NK-HDAC-1 on breast cancer in vitro and in vivo. The inhibitory effects of NK-HDAC-1 on HDAC enzyme activity and cell growth were more potent compared to suberoylanilide hydroxamic acid (SAHA). NK-HDAC-1 caused G1 cell cycle arrest at concentrations below 0.2 µM and G2/M arrest at concentrations above 0.4 µM through p21 upregulation and cyclin D1 downregulation. NK-HADC-1 induced hyperacetylation of histone H3 and H4 around the promoter region of p21. NK-HDAC-1 promoted apoptosis in MDA-MB‑231 breast cancer cells by activating both the intrinsic and the extrinsic pathway NK-HDAC-1 at doses of 3, 10 and 30 mg/kg reduced the tumor volume in MDA-MB‑231 xenografts by 25.9, 48.8 and 63.6%, respectively. The results suggested that NK-HDAC-1 may be a promising therapeutic candidate in treating human breast cancer.

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