Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line

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• 作者：Arunachalam Kalaiarasi ; Chidambaram Anusha ; Renu Sankar ; Subbiah Rajasekaran ; Jayaraj John Marshal ; Karthikeyan Muthusamy ; Vilwanathan Ravikumar
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2016
• 出版时间：December 21, 2016
• 年：2016
• 卷：64
• 期：50
• 页码：9542-9550
• 全文大小：496K
• ISSN：1520-5118

文摘

Histone deacetylases (HDACs) are a group of epigenetic enzymes that control gene expression through their repressive influence on histone deacetylation transcription. HDACs are probable therapeutic targets for cancer treatment, spurring the progress of different types of HDAC inhibitors. Further, natural-source-based derived bioactive compounds possess HDAC inhibitor property. In this way, we hypothesized that plant isoquinoline alkaloid berberine (BBR) could be a HDAC inhibitor in the human lung cancer A549 cell line. BBR represses total HDAC and also class I, II, and IV HDAC activity through hyperacetylation of histones. Furthermore, BBR triggers positive regulation of the sub-G₀/G₁ cell cycle progression phase in A549 cells. Moreover, BBR-induced A549 cell growth arrest and morphological changes were confirmed using different fluorescence-dye-based microscope techniques. Additionally, BBR downregulates oncogenes (TNF-α, COX-2, MMP-2, and MMP-9) and upregulates tumor suppressor genes (p21 and p53) mRNA and protein expressions. Besides, BBR actively regulates Bcl-2/Bax family proteins and also triggered the caspase cascade apoptotic pathway in A549 cells. Our finding suggests that BBR mediates epigenetic reprogramming by HDAC inhibition, which may be the key mechanism for its antineoplastic activity.