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

الملخص EN

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.