Thursday, May 05, 2011

Taiwanese Green Propolis Extract Propolin G Shows Anticancer Activity

NBM-HD-3, a Novel Histone Deacetylase Inhibitor with Anticancer Activity Through Modulation of PTEN and AKT in Brain Cancer Cells
J Ethnopharmacol, 2011 Apr 20

ETHNOPHARMACOLOGICAL RELEVANCE: Taiwanese green propolis (TGP) extract contains a variety of chemical components and has proven to have broad-spectrum biological activities, including anticancer, antioxidant, and antimicrobial activities. Propolin G, an active anticancer component of TGP, was isolated and characterized in this study.

AIM OF THE STUDY: Histone deacetylase inhibitors (HDACis) have been shown to be effective anticancer agents. The aim of this study was to develop a novel HDACi and investigate its anticancer mechanism.

MATERIALS AND METHODS: NBM-HD-3, a novel HDACi, was derived from propolin G. Two brain cancer cell lines (c6 and DBTRG-05MG) were used in the anti-proliferation assay. NBM-HD-3 treated cells were analyzed by flow cytometry in the cell cycle assay. The gene expression of NBM-HD-3 treated cells was determined by real-time quantitative PCR. HDAC enzyme assay, confocal microscopy and Western blot assay were used to validate NMB-HD-3 as HDACi. Western blot assay was used for analyzing cell cycle modulation by PTEN and AKT.

RESULTS: NBM-HD-3 was found to have potent anti-proliferative activity in brain cancer cells (rat C6 glioma and human DBTRG-05MG glioblastoma). Western blot analysis and HDAC enzyme assay indicated that NBM-HD-3 was an HDAC inhibitor. The Western blot data exhibited increased levels of p21, Ac-histone 3, Ac-histone 4, and Ac-tubulin after brain cancer cells being treated with NBM-HD-3. NBM-HD-3 also affected the cell cycle regulators such as p21 and cyclin B1. In the study for its anticancer mechanism, NBM-HD-3 was found to increase PTEN and AKT protein levels significantly, while decreasing p-PTEN and p-AKT levels markedly.

CONCLUSION: This study demonstrated that the novel compound, NBM-HD-3, is a potent HDAC inhibitor. It produces anticancer activity through modulation of PTEN and AKT in brain cancer cells.

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