Journal Article

NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

Lee, Cheng-Feng, Chen, Chia-Nan, Lin, Chia-Wei, Huang, Wei-Jan, Lee, Chi-Yun, Huang, Jing-Shi, Chuang, Shuang-En, Huang, Chung-Yang, Chi, Li-Ling, Chen, Ai-Ling, Liang, Yu-Chih, Chiu, Chun-Jung

2012

Overview

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50 ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21(Waf1/Cip1) gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo.

• Publisher: Hindawi Publishing Corporation,John Wiley & Sons, Inc
• Subject: AKT protein / Antitumor activity / Antitumor agents / Brain cancer / Breast cancer / Cancer therapies / Cell cycle / Chromatin / Cip protein / Cyclin B1 / Cyclin-dependent kinase inhibitor p21 / DNA methylation / Gelsolin / Gene expression / Glioma cells / Histone deacetylase / p53 Protein / Propolis / PTEN protein / Semisynthesis / Tubulin / Xenografts