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Articles by A Ahmad
Total Records ( 2 ) for A Ahmad
  A Ahmad , Y Zhang and X. F. Cao

Epigenetics refers to the study of heritable changes in gene expression or cellular phenotype without changes in DNA sequence. Epigenetic regulation of gene expression is accomplished by DNA methylation, histone modifications, histone variants, chromatin remodeling, and may involve small RNAs. DNA methylation at cytosine is carried out by enzymes called DNA Methyltransferases and is involved in many cellular processes, such as silencing of transposable elements and pericentromeric repeats, X-chromosome inactivation and genomic imprinting, etc. Histone modifications refer to posttranslational covalent attachment of chemical groups onto histones such as phosphorylation, acetylation, and methylation, etc. Histone variants, the non-canonical histones with amino acid sequences divergent from canonical histones, can have different epigenetic impacts on the genome from canonical histones. Higher-order chromatin structures maintained or modified by chromatin remodeling proteins also play important roles in regulating gene expression. Small non-coding RNAs play various roles in the regulation of gene expression at pre- as well as posttranscriptional levels. A special issue of Molecular Plant on ‘Epigenetics and Plant Development’ (Volume 4, Number 2, 2009) published a variety of articles covering many aspects of epigenetic regulation of plant development. We have tried here to present a bird's-eye view of these credible efforts towards understanding the mysterious world of epigenetics. The majority of the articles are about the chromatin modifying proteins, including histone modifiers, histone variants, and chromatin remodeling proteins that regulate various developmental processes, such as flowering time, vernalization, stem cell maintenance, and response to hormonal and environmental stresses, etc. Regulation of expression of seed transcriptome, involvement of direct tandem repeat elements in the PHE1 imprinting in addition to PcG proteins activity, paramutation, and epigenetic barriers in species hybridization are described well. The last two papers are about the Pol V-mediated heterochromatin formation independent of the 24nt-siRNA and the effect of genome position and tissue type on epigenetic regulation of gene expression. These findings not only further our current understanding of epigenetic mechanisms involved in many biological phenomena, but also pave the path for the future work, by raising many new questions that are discussed in the following lines.

  S Nazeem , A. S Azmi , S Hanif , A Ahmad , R. M Mohammad , S. M Hadi and K. S. Kumar

Plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica has been shown to exert anticancer and anti-proliferative activities in cells in culture as well as animal tumor models. In our previous paper, we have reported the cytotoxic action of plumbagin in plasmid pBR322 DNA as well as human peripheral blood lymphocytes through a redox mechanism involving copper. Copper has been shown to be capable of mediating the action of several plant-derived compounds through production of reactive oxygen species (ROS). The objective of the present study was to determine whether plumbagin induces apoptosis in human cancer cells through the same mechanism which we proposed earlier. Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, 3-(4,5-B-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for cell growth inhibition, histone/DNA ELISA, homogeneous caspase-3/7 assay for apoptosis as well as alkaline comet assay for DNA single-strand breaks detection in this report, we confirm that plumbagin causes effective cell growth inhibition, induces apoptosis and generates single-strand breaks in cancer cells. Incubation of cancer cells with scavengers of ROS and neocuproine inhibited the cytotoxic action of plumbagin proving that generation of ROS and Cu(I) are the critical mediators in plumbagin-induced cell growth inhibition. This study is the first to investigate the copper-mediated anticancer mechanism of plumbagin in human cancer cells and these properties of plumbagin could be further explored for the development of anticancer agents with higher therapeutic indices, especially for skin cancer.

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