NBM-HD-3, a novel histone deacetylase inhibitor with anticancer activity through modulation of PTEN and AKT in brain cancer cells

Wei Jan Huang, Chia Wei Lin, Chi Yun Lee, Li Ling Chi, Yi Chen Chao, Hsien Ning Wang, Bi Lian Chiou, Tzu Jung Chen, Chung Yang Huang, Chia Nan Chen

研究成果: 雜誌貢獻文章同行評審

22 引文 斯高帕斯(Scopus)

摘要

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. 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.

原文英語
頁(從 - 到)156-167
頁數12
期刊Journal of Ethnopharmacology
136
發行號1
DOIs
出版狀態已發佈 - 六月 14 2011

ASJC Scopus subject areas

  • 藥理
  • 藥物發現

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