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Vilwanathan Ravikumar - One of the best experts on this subject based on the ideXlab platform.
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plant Isoquinoline Alkaloid berberine exhibits chromatin remodeling by modulation of histone deacetylase to induce growth arrest and apoptosis in the a549 cell line
Journal of Agricultural and Food Chemistry, 2016Co-Authors: Arunachalam Kalaiarasi, Chidambaram Anusha, Renu Sankar, Subbiah Rajasekaran, Jayaraj John Marshal, Karthikeyan Muthusamy, Vilwanathan RavikumarAbstract: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 ...
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Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line
2016Co-Authors: Arunachalam Kalaiarasi, Chidambaram Anusha, Renu Sankar, Subbiah Rajasekaran, Jayaraj John Marshal, Karthikeyan Muthusamy, Vilwanathan RavikumarAbstract: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
Renu Sankar - One of the best experts on this subject based on the ideXlab platform.
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plant Isoquinoline Alkaloid berberine exhibits chromatin remodeling by modulation of histone deacetylase to induce growth arrest and apoptosis in the a549 cell line
Journal of Agricultural and Food Chemistry, 2016Co-Authors: Arunachalam Kalaiarasi, Chidambaram Anusha, Renu Sankar, Subbiah Rajasekaran, Jayaraj John Marshal, Karthikeyan Muthusamy, Vilwanathan RavikumarAbstract: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 ...
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Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line
2016Co-Authors: Arunachalam Kalaiarasi, Chidambaram Anusha, Renu Sankar, Subbiah Rajasekaran, Jayaraj John Marshal, Karthikeyan Muthusamy, Vilwanathan RavikumarAbstract: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
Takashi Morishige - One of the best experts on this subject based on the ideXlab platform.
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molecular characterization of o methyltransferases involved in Isoquinoline Alkaloid biosynthesis in coptis japonica
Proceedings of the Japan Academy. Series B Physical and biological sciences, 2010Co-Authors: Takashi Morishige, Masanori Tamakoshi, Tomoya TakemuraAbstract:O-Methyltransferases, which catalyze the production of small molecules in plants, play a crucial role in determining biosynthetic pathways in secondary metabolism because of their strict substrate specificity. Using three O-methyltransferase (OMT) cDNAs that are involved in berberine biosynthesis, we investigated the structure that was essential for this substrate specificity and the possibility of creating a chimeric enzyme with novel substrate specificity. Since each OMT has a relatively well-conserved C-terminal putative S-adenosyl-L-methionine-binding domain, we first exchanged the N-terminal halves of different OMTs. Among the 6 combinations that we tested for creating chimeric OMTs, 5 constructs produced detectable amounts of recombinant proteins, and only one of these with an N-terminal half of 6-OMT and a C-terminal half of 4'-OMT (64'-OMT) showed methylation activity with Isoquinoline Alkaloids as a substrate. Further enzymological analysis of 64'-OMT reaction product indicated that 64'-OMT retained the regio-specificity of 6-OMT. Further examination of the N-terminal region of 64'-OMT showed that about 90 amino acid residues in the N-terminal half were critical for reaction specificity. The creation of OMTs with novel reactivity is discussed.
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transient rna silencing of scoulerine 9 o methyltransferase expression by double stranded rna in coptis japonica protoplasts
Bioscience Biotechnology and Biochemistry, 2005Co-Authors: Joseph G Dubouzet, Nanae Fujii, Takashi Morishige, A N Chungil, Eiichiro Fukusaki, Kentaro IfukuAbstract:RNAi (RNA interference, RNA silencing) is a powerful tool for functional genomics, but the construction of an RNAi vector(s) and the establishment of stable transformants are time-consuming and laborious. Here we report the transient RNAi of endogenous biosynthetic genes involved in Isoquinoline Alkaloid biosynthesis in Coptis japonica protoplasts. Double stranded (ds) RNA fragments of various lengths prepared from several different positions of the coding sequence of scoulerine 9-O-methyltransferase (SMT) were introduced into C. japonica protoplasts by polyethylene glycol-mediated transformation, and their effects were monitored by reverse transcription-polymerase chain reaction. Substantial silencing of SMT gene expression was obtained by the introduction of these SMT dsRNAs. A significant reduction in SMT protein levels was also observed. The potentials of this transient RNAi system to evaluate the functions of biosynthetic genes in Coptis Alkaloid research are discussed.
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Molecular cloning of columbamine O-methyltransferase from cultured Coptis japonica cells.
FEBS Journal, 2002Co-Authors: Takashi Morishige, Emilyn G Dubouzet, Kum Boo ChoiAbstract:To identify all of the O-methyltransferase genes involved in Isoquinoline Alkaloid biosynthesis in Coptis japonica cells, we sequenced 1014 cDNA clones isolated from high-Alkaloid-producing cultured cells of C. japonica. Among them, we found all three reported O-methyltransferases and an O-methyltransferase-like cDNA clone (CJEST64). This cDNA was quite similar to S-adenosyl-l-methionine:coclaurine 6-O-methyltransferase and S-adenosyl-l-methionine:isoflavone 7-O-methyltransferase. As S-adenosyl-l-methionine:columbamine O-methyltransferase, which catalyzes the conversion of columbamine to palmatine, is one of the remaining unelucidated components in Isoquinoline Alkaloid biosynthesis in C. japonica, we heterologously expressed the protein in Escherichia coli and examined the activity of columbamine O-methyltransferase. The recombinant protein clearly showed O-methylation activity using columbamine, as well as (S)-tetrahydrocolumbamine, (S)-, (R,S)-scoulerine and (R,S)-2,3,9,10-tetrahydroxyprotoberberine as substrates. This result clearly indicated that EST analysis was useful for isolating the candidate gene in a relatively well-characterized biosynthetic pathway. The relationship between the structure and substrate recognition of the O-methyltransferases involved in Isoquinoline Alkaloid biosynthesis, and a reconsideration of the biosynthetic pathway to palmatine are discussed.
Michel Frederich - One of the best experts on this subject based on the ideXlab platform.
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revealing the anti tumoral effect of algerian glaucium flavum roots against human cancer cells
Phytomedicine, 2013Co-Authors: Sihem Bensalem, Fadila Maizabenabdesselam, Fatiha Bedjou, Paul Peixoto, Arnaud Gonzalez, Monique Tits, Jean-noël Wauters, Michel FrederichAbstract:Abstract Glaucium flavum ( G. flavum ) is a plant from the Papaveraceae family native to Algeria where it is used in local traditional medicine to treat warts. G. flavum root crude Alkaloid extract inhibited breast cancer cell proliferation and induced G2/M phase cycle arrest and apoptosis without affecting normal cells, which is a highly awaited feature of potential anti-cancer agents. G. flavum significantly reduced growth and vascularization of human glioma tumors on chicken chorioallantoic membrane (CAM) in vivo. The chromatographic profile of the dichloromethane extract of G. flavum root showed the presence of different constituents including the Isoquinoline Alkaloid protopine, as the major compound. We report for the first time that G. flavum extract may represent a new promising agent for cancer chemotherapy.
Scott M Laster - One of the best experts on this subject based on the ideXlab platform.
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inhibition of h1n1 influenza a virus growth and induction of inflammatory mediators by the Isoquinoline Alkaloid berberine and extracts of goldenseal hydrastis canadensis
International Immunopharmacology, 2011Co-Authors: Chad E Cecil, Jeanine M Davis, Scott M LasterAbstract:In this study we tested whether the Isoquinoline Alkaloid berberine can inhibit the growth of influenza A. Our experiments showed strong inhibition of the growth of H1N1 influenza A strains PR/8/34 or WS/33 in RAW 264.7 macrophage-like cells, A549 human lung epithelial-derived cells and murine bone marrow derived macrophages, but not MDCK canine kidney cells. Studies of the mechanism underlying this effect suggest that berberine acts post-translationally to inhibit virus protein trafficking/maturation which in turn inhibits virus growth. Berberine was also evaluated for its ability to inhibit production of TNF-a and PGE2 from A/PR/8/34 infected-RAW 264.7 cells. Our studies revealed strong inhibition of production of both mediators and suggest that this effect is distinct from the anti-viral effect. Finally, we asked whether berberine-containing ethanol extracts of goldenseal also inhibit the growth of influenza A and production of inflammatory mediators. We found strong effectiveness at high concentrations, although upon dilution extracts were somewhat less effective than purified berberine. Taken together, our results suggest that berberine may indeed be useful for the treatment of infections with influenza A.