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: Wei-Jan Huang, Yu-Chih Liang, Shuang-En Chuang, Li-Ling Chi, Chi-Yun Lee, Chia-Wei Lin, Ai-Ling Chen, Jing-Shi Huang, Chun-Jung Chiu, Cheng-Feng Lee, Chung-Yang Huang, Chia-Nan Chen
• Journal: Evidence-based complementary and alternative medicine : eCAM (Evid Based Complement Alternat Med) Vol. 2012 Pg. 781417 ( 2012) ISSN: 1741-4288 [Electronic] United States
• PMID: 22046195 (Publication Type: Journal Article)