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https://www.readbyqxmd.com/read/28103535/down-regulation-of-histone-deacetylase-4-5-and-6-as-a-mechanism-of-synergistic-enhancement-of-apoptosis-in-human-lung-cancer-cells-treated-with-the-combination-of-a-synthetic-retinoid-am80-and-green-tea-catechin
#1
Yukiko Oya, Anupom Mondal, Anchalee Rawangkan, Sonthaya Umsumarng, Keisuke Iida, Tatsuro Watanabe, Miki Kanno, Kaori Suzuki, Zhenghao Li, Hiroyuki Kagechika, Koichi Shudo, Hirota Fujiki, Masami Suganuma
(-)-Epigallocatechin gallate (EGCG), a green tea catechin, acts as a synergist with various anticancer drugs, including retinoids. Am80 is a synthetic retinoid with a different structure from all-trans-retinoic acid: Am80 is now clinically utilized as a new drug for relapsed and intractable acute promyelocytic leukemia patients. Our experiments showed that the combination of EGCG and Am80 synergistically induced both apoptosis in human lung cancer cell line PC-9 and up-regulated expressions of growth arrest and DNA damage-inducible gene 153 (GADD153), death receptor 5, and p21(waf1) genes in the cells...
January 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28103177/hbxip-a-binding-protein-of-hbx-regulates-maintenance-of-the-g2-m-phase-checkpoint-induced-by-dna-damage-and-enhances-sensitivity-to-doxorubicin-induced-cytotoxicity
#2
Hong-Rong Fei, Yun-Sheng Zhou, Ruo-Tong Li, Ming-Feng Yang, Jian Ma, Feng-Ze Wang
To maintain the integrity of the genome, cells need to detect and repair DNA damage before they complete cell division. Hepatitis B x-interacting protein (HBXIP), a binding protein of HBx (Hepatitis B virus x protein), is aberrantly overexpressed in human cancer cells and show to promote cell proliferation and inhibit apoptosis. The present study is designed to investigate the role of HBXIP on the DNA damage response. Our results show that HBXIP acts as an important regulator of G2/M checkpoint in response to DNA damage...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28103133/role-of-choline-in-the-modulation-of-degenerative-processes-in-vivo-and-in-vitro-studies
#3
Tania Merinas-Amo, Inmaculada Tasset-Cuevas, Antonio M Díaz-Carretero, Ángeles Alonso-Moraga, Fernando Calahorro
The purpose of the present study was to examine the nutraceutical potential of choline as an added value to its well-known brain nutrient role. Several toxicity, antitoxicity, genotoxicity, antigenotoxicity, and longevity endpoints were checked in the somatic mutation and recombination test in in vivo Drosophila animal model. Cytotoxicity in human leukemia-60 cell line (HL-60) promyelocytic and NIH3T3 mouse fibroblast cells, proapoptotic DNA fragmentation, comet assay, methylation status, and macroautophagy (MA) activity were tested in in vitro assays...
January 19, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28103122/ptk2-mediated-degradation-of-atg3-impedes-cancer-cells-susceptible-to-dna-damage-treatment
#4
Ke Ma, Wan Fu, Ming Tang, Chaohua Zhang, Tianyun Hou, Ran Li, Xiaopeng Lu, Yanan Wang, Jingyi Zhou, Xue Li, Luyao Zhang, Lina Wang, Ying Zhao, Wei-Guo Zhu
ATG3 (autophagy related 3) is an E2-like enzyme essential for autophagy; however, it is unknown whether it has an autophagy-independent function. Here, we report that ATG3 is a relatively stable protein in unstressed cells, but it is degraded in response to DNA-damaging agents such as etoposide or cisplatin. With mass spectrometry and a mutagenesis assay, phosphorylation of tyrosine 203 of ATG3 was identified to be a critical modification for its degradation, which was further confirmed by manipulating ATG3(Y203E) (phosphorylation mimic) or ATG3(Y203F) (phosphorylation-incompetent) in Atg3 knockout MEFs...
January 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#5
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28102315/methyl-cytosine-driven-structural-changes-enhance-adduction-kinetics-of-an-exon-7-fragment-of-the-p53-gene
#6
Spundana Malla, Karteek Kadimisetty, You-Jun Fu, Dharamainder Choudhary, John B Schenkman, James F Rusling
Methylation of cytosine (C) at C-phosphate-guanine (CpG) sites enhances reactivity of DNA towards electrophiles. Mutations at CpG sites on the p53 tumor suppressor gene that can result from these adductions are in turn correlated with specific cancers. Here we describe the first restriction-enzyme-assisted LC-MS/MS sequencing study of the influence of methyl cytosines (MeC) on kinetics of p53 gene adduction by model metabolite benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), using methodology applicable to correlate gene damage sites for drug and pollutant metabolites with mutation sites...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101907/increased-arf-p53-activity-in-stem-cells-aging-and-cancer
#7
REVIEW
Estefania Carrasco-Garcia, Manuel Moreno, Leire Moreno-Cugnon, Ander Matheu
Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration...
January 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28101820/insulin-insulin-like-growth-factor-1-signalling-iis-based-regulation-of-lifespan-across-species
#8
REVIEW
Rebecca Mathew, Manika Pal Bhadra, Utpal Bhadra
An organism's well-being is facilitated by numerous molecular and biochemical pathways that ensure homeostasis within cells and tissues. Aging causes a gradual let-down in the maintenance of homeostasis due to various endogenous and environmental challenges, leading to amassing of damages, functional deterioration of different tissues and vulnerability to ailments. Nutrient sensing pathways that maintain glucose homeostasis in body are involved in regulation of aging. Insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) pathway was the first nutrient sensing pathway discovered to affect the aging process...
January 18, 2017: Biogerontology
https://www.readbyqxmd.com/read/28101326/microhomology-mediated-end-joining-new-players-join-the-team
#9
REVIEW
Hailong Wang, Xingzhi Xu
DNA double-strand breaks (DSBs) are the most deleterious type of DNA damage in cells arising from endogenous and exogenous attacks on the genomic DNA. Timely and properly repair of DSBs is important for genomic integrity and survival. MMEJ is an error-prone repair mechanism for DSBs, which relies on exposed microhomologous sequence flanking broken junction to fix DSBs in a Ku- and ligase IV-independent manner. Recently, significant progress has been made in MMEJ mechanism study. In this review, we will summarize its biochemical activities of several newly identified MMEJ factors and their biological significance...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28100855/trace-elements-as-an-activator-of-antioxidant-enzymes
#10
Marta Wołonciej, Elżbieta Milewska, Wiesława Roszkowska-Jakimiec
Oxidative stress is a state of impaired balance between the formation of free radicals and antioxidant capacity of the body. It causes many defects of the body, e.g. lipid peroxidation, DNA and protein damage. In order to prevent the effects of oxidative stress, the organism has developed defence mechanisms. These mechanisms capture and inhibit the formation of free radicals and also chelate ion metals that catalyse free radical reactions. Trace elements are components of antioxidant enzymes involved in antioxidant mechanisms...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100701/self-cytoplasmic-dna-upregulates-the-mutator-enzyme-apobec3a-leading-to-chromosomal-dna-damage
#11
Rodolphe Suspène, Bianka Mussil, Hélène Laude, Vincent Caval, Noémie Berry, Mohamed S Bouzidi, Valérie Thiers, Simon Wain-Hobson, Jean-Pierre Vartanian
Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28100636/centriole-splitting-caused-by-loss-of-the-centrosomal-linker-protein-c-nap1-reduces-centriolar-satellite-density-and-impedes-centrosome-amplification
#12
Anne-Marie Flanagan, Elena Stavenschi, Shivakumar Basavaraju, David Gaboriau, David A Hoey, Ciaran G Morrison
Duplication of the centrosomes is a tightly regulated process. Abnormal centrosome numbers can impair cell division and cause changes in how cells migrate. Duplicated centrosomes are held together by a proteinaceous linker made up of rootletin filaments anchored to the centrioles by C-NAP1. This linker is removed in a NEK2A kinase-dependent manner as mitosis begins. To explore C-NAP1 activities in regulating centrosome activities, we used genome editing to ablate it. C-NAP1 null cells were viable and had an increased frequency of premature centriole separation, accompanied by reduced density of the centriolar satellites, with re-expression of C-NAP1 rescuing both these phenotypes...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28100624/azacytidine-treatment-inhibits-the-progression-of-herpes-stromal-keratitis-by-enhancing-regulatory-t-cell-function
#13
Siva Karthik Varanasi, Pradeep B J Reddy, Siddheshvar Bhela, Ujjaldeep Jaggi, Fernanda Gimenez, Barry T Rouse
: Ocular infection with Herpes Simplex Virus type 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance as well as chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit Stromal Keratitis (SK) lesion severity. In this report, we have explored the novel approach of inhibiting DNA methyltransferase activity using 5-Azacytidine (cytosine analog) to limit HSV-1 induced ocular lesions...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100588/involvement-of-conserved-amino-acids-in-the-c-terminal-region-of-line-1-orf2p-in-retrotransposition
#14
Claiborne M Christian, Mark Sokolowski, Dawn deHaro, Kristine J Kines, Victoria P Belancio
Long Interspersed Element 1 (LINE-1 or L1) is the only currently active autonomous retroelement in the human genome. Along with the parasitic SVA and SINE Alu, L1 is the source of DNA damage induced by retrotransposition, a copy-and-paste process that has the potential to disrupt gene function and cause human disease. The retrotransposition process is dependent upon the ORF2 protein (ORF2p). However, it is unknown whether most of the protein is important for retrotransposition. In particular, other than the Cys motif, the C-terminus of the protein has not been intensely examined in the context of retrotransposition...
January 18, 2017: Genetics
https://www.readbyqxmd.com/read/28100347/-salvianolate-protects-h9c2-cells-from-hypoxia-reoxygenation-injury-induced-apoptosis-by-attenuating-mitochondrial-dna-oxidative-damage
#15
R C Yue, X L Yang, R Y Zhang, S Liu, J Liu, J Zeng, H Liang, W Wang, H X Hu, C Y Zeng
Objective: To investigate the possible mechanism related to the protective effects of salvianolate in H9c2 cells underwent hypoxia/reoxygenation (H/R)-injury. Methods: H9c2 cells were divided into four groups: control group, salvianolate group (S group), H/R group, and salvianolate+ H/R group(S+ H/R group), in which the H9c2 cells were pretreated with salvianolate before H/R-treatment.Apoptotic cells were detected by Tunel assays and AnnexinⅤ-FITC apoptosis detection kit.The intracellular ATP level, the change of mitochondrial membrane potential and the mitochondrial DNA oxidative damage were also determined in these groups...
January 25, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28100096/targeting-therapy-resistant-cancer-stem-cells-by-hyperthermia
#16
A L Oei, L E M Vriend, P M Krawczyk, M R Horsman, N A P Franken, J Crezee
Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumor that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells (CSCs), is considered to be of particular significance for tumor initiation, progression and metastasis. CSCs are considered in particular to be therapy-resistant and may drive disease recurrence, which positions CSCs in the focus of anti-cancer research, but successful CSC-targeting therapies are limited...
January 19, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28100039/low-dose-radiation-causes-skin-cancer-in-mice-and-has-a-differential-effect-on-distinct-epidermal-stem-cells
#17
Tatiana Revenco, Gaelle Lapouge, Virginie Moers, Sylvain Brohée, Panagiota A Sotiropoulou
The carcinogenic effect of ionizing radiation has been evaluated based on limited populations accidently exposed to high dose radiation. In contrast, insufficient data are available on the effect of low dose radiation, such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that low dose radiation results in DNA damage in sebaceous gland and bulge epidermal stem cells (SCs)...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28099941/the-roles-of-rrp15-in-nucleolar-formation-ribosome-biogenesis-and-checkpoint-control-in-human-cells
#18
Zhixiong Dong, Changjun Zhu, Qimin Zhan, Wei Jiang
The nucleolus controls ribosome biogenesis and its perturbation induces nucleolar stress that inhibits cell cycle progression and activates checkpoint responses. Here, we investigate the roles of ribosomal RNA processing protein, RRP15, in nucleolar formation, ribosome biogenesis, cell cycle progression and checkpoint control in human cells. RRP15 is localized in the nucleolus and required for nucleolar formation. In contrast to the budding yeast Rrp15p that was reported as a component of pre-60S subunits, RRP15 is found in both pre-40S and pre-60S subunits and involved in regulating rRNA transcription and ribosome biogenesis...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#19
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099512/age-dependent-oxidative-dna-damage-does-not-correlate-with-reduced-proliferation-of-cardiomyocytes-in-humans
#20
Yanhui Huang, Haifa Hong, Minghui Li, Jinfen Liu, Chuan Jiang, Haibo Zhang, Lincai Ye, Jinghao Zheng
BACKGROUND: Postnatal human cardiomyocyte proliferation declines rapidly with age, which has been suggested to be correlated with increases in oxidative DNA damage in mice and plays an important role in regulating cardiomyocyte proliferation. However, the relationship between oxidative DNA damage and age in humans is unclear. METHODS: Sixty right ventricular outflow myocardial tissue specimens were obtained from ventricular septal defect infant patients during routine congenital cardiac surgery...
2017: PloS One
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