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Garcinia indica (Kokum) and Ilex aquifolium (European Holly)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Dicson Sheeja Malar, Mani Iyer Prasanth, Tewin Tencomnao, James Michael Brimson, Anchalee Prasansuklab
The ethyl acetate extract of I. aquifolium leaves exhibits anticancer activity against colon carcinoma cells and glioblastoma cells (Frédérich et al., 2009). UA, the bioactive component of I. aquifolium exhibits potential anticancer effects. It inhibits angiogenesis, invasion, and migration of NSCLC cells by attenuating programmed death ligand-1 (PD-L1) expression, that mediates metastasis through the EGFR/JAK2/STAT3 pathway (Kang et al., 2021). Invasion of lung cancer cells was inhibited by the diminution of epithelial–mesenchymal transition by downregulating the expression of astrocyte-elevated gene-1 (AEG-1) by targeting NFκB pathway (Liu et al., 2013). Further, UA attenuated the expression of DNMT1 and EZH2, which are involved in tumor progression through SAP/JNK pathway (Wu et al., 2015). In NSCLC cells with EGFR T790M mutations, UA suppressed the expression of the proto-oncogene CT45A2 gene, which is involved in tumorigenesis through β‐catenin/TCF4 signaling pathway (Yang et al., 2019). Moreover, UA increased the sensitivity of chemoresistant NSCLC cells by inhibiting miR-149-5p/MyD88 signaling (Chen et al., 2020a). UA specifically binds and inhibits activity of vaccinia-related kinase 1 (VRK1) kinase domain and induces DNA damage in lung cancer cells (Kim et al., 2015).
DNA methylation analysis using bisulfite sequencing data
Published in Altuna Akalin, Computational Genomics with R, 2020
DNA methylation is established by DNA methyltransferases DNMT3A and DNMT3B in combination with DNMT3L and maintained through cell division by the methyltransferase DNMT1 and associated proteins. DNMT3a and DNMT3b are in charge of the de novo methylation during early development. Loss of 5mC can be achieved passively by dilution during replication or exclusion of DNMT1 from the nucleus. Recent discoveries of the ten-eleven translocation (TET) family of proteins and their ability to convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) in vertebrates provide a path for catalyzed active DNA demethylation (Tahiliani et al., 2009). Iterative oxidations of 5hmC catalyzed by TET result in 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). 5caC mark is excised from DNA by G/T mismatch-specific thymine-DNA glycosylase (TDG), which as a result reverts cytosine residue to its unmodified state (He et al., 2011). Apart from these, mainly bacteria, but possibly higher eukaryotes, contain base modifications on bases other than cytosine, such as methylated adenine or guanine (Clark et al., 2011).
Methylome and epigenetic markers
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Skevi Kyriakou, Marios Ioannides, George Koumbaris, Philippos Patsalis
DNA methylation is mediated by DNA methyl transferases (DNMT), which are enzymes responsible for catalyzing, recognizing, adding, and removing methyl groups. They are separated into two main classes: writers and erasers. Writers catalyze the addition of the methyl group onto cytosine residues, and erasers are associated with methyl group modification and removal. Specifically, DNMT1 is responsible for maintaining the heritable methyl group on the cytosine residues and has a preference for hemimethylated CpG sites generated by DNA replication (5). DNMT3A and DNMT3B are de novo methyltransferases responsible for methylating CpGs missed by DNMT1 (6,7). When DNA demethylation is required, either a passive or an active demethylation process takes place. Passive demethylation involves the inhibition of DNMT1 during cell replication in dividing cells. Active DNA demethylation involves enzymatic reactions to remove the methyl group from the cytosine residues, and it occurs in both dividing and nondividing cells (8). This mechanism allows for the embryonic development by controlling expression of genes at specific times and tissues.
Design, synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Ennian Li, Kai Wang, Bei Zhang, Siqi Guo, Senhao Xiao, Qi Pan, Xiaowan Wang, Weiying Chen, Yunshan Wu, Hesong Xu, Xiangqian Kong, Cheng Luo, Shijie Chen, Bo Liu
Epigenetic modification, like DNA methylation, plays a major role in the expression of genetic information. Methylation of DNA at C-5 of cytosine is one of the most studied modifications of the mammalian genome1. DNMTs (DNA methyltransferases), which include DNMT1, DNMT3A, and DNMT3B, have been identified in humans2. DNMT1 is the most abundant among the three and is responsible for the maintenance of CpG methylation patterns in mammals with hemimethylated CpG dinucleotides serving as preferred substrates3. DNMT1 plays a significant role in the structural modification of chromosomes and the regulation of gene expression1. The methylation of the 5-carbon on cytosine residues (5mC) in CpG dinucleotides was the first described covalent modification of DNA and is one of the most extensively characterised modifications of chromatin, and thus, DNMT inhibitors have become useful tools for treating cancers4.
Zinc affects nuclear factor kappa b and DNA methyltransferase activity in C3H cancer fibroblast cells induced by a 2100 MHz electromagnetic field
Published in Electromagnetic Biology and Medicine, 2022
D. Duzgun Ergun, N. Pastaci Ozsobaci, T. Yilmaz, D. Ozcelik, M. T. Kalkan
Exploration of DNA methylation changes in cancer development is of great importance in the development of new agents for cancer treatment. The DNMT inhibitors have become a target in cancer treatment due to their effects on epigenetic mechanisms. The DNMT inhibitors have been supported with various dietary supplements can exert an anti-proliferative effect (Gros et al. 2012; Yusuf et al. 2021). Zn plays an important role in cell proliferation, regulation of DNA synthesis, cell growth and development, the activation of NF-κB. It is stated that the overexpression of NF-κB can activate cancer-related pathways. It has been reported that intracellular Zn homeostasis affects DNA methylation, which has played a role in the prevention and suppression of cancer development, and thus intracellular Zn balance should be kept under control. In our study, we aimed to evaluate the response of cancer cells exposed to the EMF emitted by mobile phones and the effects of Zn supplementation. In order to evaluate the effect of Zn on C3H cancer fibroblast cells exposed to 2100 MHz EMF, we analyzed cell viability %, NF-κB and DNMT activities.
Fumarate hydratase as a therapeutic target in renal cancer
Published in Expert Opinion on Therapeutic Targets, 2020
Priyanka Kancherla, Michael Daneshvar, Rebecca A. Sager, Mehdi Mollapour, Gennady Bratslavsky
As previously discussed, fumarate accumulation in the absence of FH results in inhibition of 2-oxoglutarate-dependent dioxygenases, specifically the TET family. TET enzymes facilitate DNA demethylation and their inhibition results in genome-wide hypermethylation with consequent alterations in gene expression [62]. Epigenetic modification via DNA methylation is a known mechanism of tumorigenesis and modulation of DNA methylation is a successful therapeutic strategy in other cancer, specifically hematologic malignancies [63]. DNA methyltransferases (DNMT) are a family of enzymes that add a methyl group to cytosine residues of DNA, altering transcription of that gene. DNMT inhibitors are a drug class that inhibit DNA methylation and thereby alter the epigenetic profile of the genome to counteract the aberrant methylation profiles seen in cancer. These inhibitors are currently approved for use in myelodysplastic syndrome and are being trialed in several other cancers [64]. Given the DNA hypermethylation seen with FH loss, an ongoing phase II clinical trial aims to evaluate the efficacy of the DNMT inhibitor, SGI-110 (guadecitabine), in patients with HLRCC-associated RCC, the results of which may reveal a novel pathway for therapeutic targeting (NCT03165721).