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

July 2013 Volume 30 Issue 1

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July 2013 Volume 30 Issue 1

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Article

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
View Affiliations / Copyright

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
Pages: 499-505
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Published online on: April 29, 2013

https://doi.org/10.3892/or.2013.2434
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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