title: NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity.
abstract: 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 IC(50) 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.
authors: Graduate Institute of Pharmacognosy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors: Wei-Jan
authors: WJ
authors: Huang
authors: Yu-Chih
authors: YC
authors: Liang
authors: Shuang-En
authors: SE
authors: Chuang
authors: Li-Ling
authors: LL
authors: Chi
authors: Chi-Yun
authors: CY
authors: Lee
authors: Chia-Wei
authors: CW
authors: Lin
authors: Ai-Ling
authors: AL
authors: Chen
authors: Jing-Shi
authors: JS
authors: Huang
authors: Chun-Jung
authors: CJ
authors: Chiu
authors: Cheng-Feng
authors: CF
authors: Lee
authors: Chung-Yang
authors: CY
authors: Huang
authors: Chia-Nan
authors: CN
authors: Chen