title: Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line.
abstract: 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/G1cell 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.
authors.affiliation: Department of Biochemistry, School of Life Sciences, Bharathidasan University , Tiruchirappalli, Tamil Nadu 620 024, India.
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Kalaiarasi
authors.affiliation: Department of Biochemistry, School of Life Sciences, Bharathidasan University , Tiruchirappalli, Tamil Nadu 620 024, India.
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Anusha
authors.affiliation: Department of Biochemistry, School of Life Sciences, Bharathidasan University , Tiruchirappalli, Tamil Nadu 620 024, India.|Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University , 1680 Madison Avenue, Wooster, Ohio 44691, United States.
authors.forename: Renu
authors.initials: R
authors.lastname: Sankar
authors.affiliation: Department of Biotechnology, Bharathidasan Institute of Technology, Anna University , Tiruchirappalli, Tamil Nadu 620 024, India.
authors.forename: Subbiah
authors.initials: S
authors.lastname: Rajasekaran
authors.affiliation: Department of Bioinformatics, Alagappa University , Karaikudi, Tamil Nadu 630 003, India.
authors.forename: Jayaraj
authors.initials: J
authors.lastname: John Marshal
authors.affiliation: Department of Bioinformatics, Alagappa University , Karaikudi, Tamil Nadu 630 003, India.
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Muthusamy
authors.affiliation: Department of Biochemistry, School of Life Sciences, Bharathidasan University , Tiruchirappalli, Tamil Nadu 620 024, India.
authors.forename: Vilwanathan
authors.identifier: http://orcid.org/0000-0003-4197-9684
authors.initials: V
authors.lastname: Ravikumar
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001599:Berberine / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D009857:Oncogenes; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D007546:Isoquinolines; D001599:Berberine; D006655:Histone Deacetylases
keywords: A549 cells; apoptosis; berberine; cell cycle; epigenetics; histone deacetylase; histone deacetylase inhibitor