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https://www.readbyqxmd.com/read/28732355/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#1
Stéphanie Arnould, Geneviève Rodier, Gisèle Matar, Charles Vincent, Nelly Pirot, Yoann Delorme, Charlène Berthet, Yoan Buscail, Jean Yohan Noël, Simon Lachambre, Marta Jarlier, Florence Bernex, Hélène Delpech, Pierre Olivier Vidalain, Yves L Janin, Charles Theillet, Claude Sardet
Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731233/integration-of-cellular-and-molecular-endpoints-to-assess-the-toxicity-of-polycyclic-aromatic-hydrocarbons-in-hepg2-cell-line
#2
Patrícia I Morgado, Sílvia Jose, Riccardo Wanke, Alexandra M M Antunes, Ana Sofia Cardoso, Luisa Jordao
Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants present in the environment with known mutagenic and carcinogenic properties. In the present study the effect of exposure to single or multiple doses of benzo[a]anthracene (BaA), pyrene (Pyr) and three halogenated derivatives of these compounds (1-ClPyr; 1-BrPyr and 7-ClBaA) were evaluated in a liver-derived human cell line (HepG2). Cytotoxicity as assessed by the classic MTT and neutral red assays showed a mild toxic effect in response to single or multiple dose exposure for up to 72h; except for multiple dose exposure to BaA and 7-ClBaA (1μM per day during 4 days) and single exposure to 10 μM BaA...
July 21, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28730515/selective-induction-of-dna-damage-g2-abrogation-and-mitochondrial-apoptosis-by-leaf-extract-of-traditional-medicinal-plant-wrightia-arborea-in-k562-cells
#3
T Lakshmipriya, T Soumya, P R Jayasree, P R Manish Kumar
Plants have proved to be an important source of anti-cancer drugs. Wrightia arborea, an Indian Ayurvedic medicinal plant, is used traditionally to treat a variety of ailments. This study evaluates the antiproliferative/apoptotic potential of Wrightia arborea leaf extracts, prepared in different organic solvents, on cancer cell lines. MTT assay, light and fluorescence microscopy, flow cytometry, DNA laddering, alkaline comet assay, and western blotting were some of the techniques used for evaluation. Combinations of camptothecin, either with CHK1 inhibitor-PD407824 or with W...
July 20, 2017: Protoplasma
https://www.readbyqxmd.com/read/28728896/platinum-iv-complexes-conjugated-with-phenstatin-analogue-as-inhibitors-of-microtubule-polymerization-and-reverser-of-multidrug-resistance
#4
Xiaochao Huang, Rizhen Huang, Shaohua Gou, Zhimei Wang, Zhixin Liao, Hengshan Wang
Pt(IV) complexes comprising a phenstatin analogue, as dual-targeting Pt(IV) prodrug, were designed and synthesized. They were found not only to carry the DNA binding platinum warhead into the tumor cells, but also to have a small molecular unit to inhibit tubulin polymerization. In vitro evaluation results revealed that Pt(IV) complexes showed better and more potent activity against the test human cancer cells including cisplatin resistant cell lines than their corresponding Pt(II) counterparts. In addition, the Pt(IV) derivative of cisplatin, complex 10, exhibited highly selective inhibition in human cancer cells and displayed no obvious toxicity to two human normal cell lines, respectively...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28725363/bridging-two-scholarly-islands-enriches-both-coi-dna-barcodes-for-species-identification-versus-human-mitochondrial-variation-for-the-study-of-migrations-and-pathologies
#5
David S Thaler, Mark Y Stoeckle
DNA barcodes for species identification and the analysis of human mitochondrial variation have developed as independent fields even though both are based on sequences from animal mitochondria. This study finds questions within each field that can be addressed by reference to the other. DNA barcodes are based on a 648-bp segment of the mitochondrially encoded cytochrome oxidase I. From most species, this segment is the only sequence available. It is impossible to know whether it fairly represents overall mitochondrial variation...
October 2016: Ecology and Evolution
https://www.readbyqxmd.com/read/28723662/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#6
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718669/fruit-peel-polyphenolic-extract-induced-apoptosis-in-human-breast-cancer-cells-is-associated-with-ros-production-and-modulation-of-p38mapk-erk1-2-and-the-akt-signaling-pathway
#7
Martin Kello, Lucia Kulikova, Janka Vaskova, Alexandra Nagyova, Jan Mojzis
Polyphenols represent a large group of natural substances with different biological properties. Currently, polyphenols are well studied due to their free radicals' scavenging and antioxidant activities. However, some studies indicate that polyphenols also exhibit pro-oxidant properties. In this study, the possible involvement of the pro-oxidant activities of fruit polyphenols was investigated in relation to apoptosis induction. To determine the type of cell death induced by fruit polyphenols (Flavine; F7), we assessed a series of assays, including measurements of caspase-7 activation, membrane mitochondrial potential changes, reactive oxygen (ROS) and nitrogen species production, lipid peroxidation, antioxidant enzymes activities, and PARP cleavage...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28714034/inhibition-of-nampt-decreases-cell-growth-and-enhances-susceptibility-to-oxidative-stress
#8
Renhua Xu, Zhenwei Yuan, Lijuan Yang, Lele Li, Dan Li, Changjun Lv
Nicotinamide adenine dinucleotide (NAD) is an essential molecule for living organisms and plays a vital role in aging and age-associated diseases. In eukaryotic cells, cellular NAD is mainly generated by the scavenge pathway in which nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the formation of nicotinamide mononucleotide. Inhibition of NAMPT is a therapeutic strategy for cancer treatment. To explore the effects of NAMPT inhibition on cellular processes, cells were treated with 10 nM FK866, an NAMPT inhibitor, resulting in a decrease in the cellular NAD level, a lower growth rate, and enhanced susceptivity to oxidative stress as compared to the untreated cells...
July 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713944/truncated-apolipoprotein-c-i-induces-apoptosis-in-neuroblastoma-by-activating-caspases-in-the-extrinsic-and-intrinsic-pathways
#9
Fei Guo, Wei Zhao, Lin Yang, Yang Yang, Saiqi Wang, Yingjun Wang, Zhaoming Li, Jiaxiang Wang
Truncated apolipoprotein C-I is a post-translationally modified protein characterized by the loss of threonine and proline residues from the N-terminus of the mature peptide. The truncated peptide is involved in many physiological and pathological processes in vivo and is related to malignant diseases. The aim of the present study was to assess the effects of the truncated peptide on tumorigenesis in neuroblastoma. The truncated peptide was chemically synthesized, and a signal peptide was used as the negative control...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713155/hypoxia-induces-universal-but-differential-drug-resistance-and-impairs-anticancer-mechanisms-of-5-fluorouracil-in-hepatoma-cells
#10
Jing-Qiu Li, Xian Wu, Lu Gan, Xiang-Liang Yang, Ze-Hong Miao
Hepatocellular carcinoma (HCC) is one of the most refractory cancers. The mechanisms by which hypoxia further aggravates therapeutic responses of advanced HCC to anticancer drugs remain to be clarified. Here, we report that hypoxia (1% O2) caused 2.55-489.7-fold resistance to 6 anticancer drugs (sorafenib, 5-fluorouracil [5-FU], gemcitabine, cisplatin, adriamycin and 6-thioguanine) in 3 HCC cell lines (BEL-7402, HepG2 and SMMC-7721). Among the 6 drugs, sorafenib, the sole one approved for HCC therapy, inhibited proliferation with little influence from hypoxia and displayed the smallest variation among the 3 HCC cell lines tested...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28706417/indole-phytoalexin-derivatives-induce-mitochondrial-mediated-apoptosis-in-human-colorectal-carcinoma-cells
#11
Viera Tischlerova, Martin Kello, Mariana Budovska, Jan Mojzis
AIM: To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODS: Changes in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28704716/transcriptional-consequences-of-xpa-disruption-in-human-cell-lines
#12
Mandira Manandhar, Megan G Lowery, Karen S Boulware, Kevin H Lin, Yue Lu, Richard D Wood
Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage...
June 29, 2017: DNA Repair
https://www.readbyqxmd.com/read/28704533/peripheral-blood-mitochondrial-dna-content-in-relation-to-circulating-metabolites-and-inflammatory-markers-a-population-study
#13
Judita Knez, Vannina G Marrachelli, Nicholas Cauwenberghs, Ellen Winckelmans, Zhenyu Zhang, Lutgarde Thijs, Jana Brguljan-Hitij, Michelle Plusquin, Christian Delles, Daniel Monleon, Josep Redón, Jan A Staessen, Tim S Nawrot, Tatiana Kuznetsova
Mitochondrial DNA (mtDNA) content might undergo significant changes caused by metabolic derangements, oxidative stress and inflammation that lead to development and progression of cardiovascular diseases. We, therefore, investigated in a general population the association of peripheral blood mtDNA content with circulating metabolites and inflammatory markers. We examined 310 subjects (50.6% women; mean age, 53.3 years) randomly selected from a Flemish population. Relative mtDNA content was measured by quantitative real-time PCR in peripheral blood cells...
2017: PloS One
https://www.readbyqxmd.com/read/28702491/data-on-the-time-of-integration-of-the-human-mitochondrial-pseudogenes-numts-into-the-nuclear-genome
#14
Konstantin Gunbin, Leonid Peshkin, Konstantin Popadin, Sofia Annis, Rebecca R Ackermann, Konstantin Khrapko
The data and methods presented in this article are supplementing the research article "Integration of mtDNA pseudogenes into the nuclear genome coincides with speciation of the human genus. A hypothesis", DOI: 10.1016/j.mito.2016.12.001 (Gunbin et al., 2017) [1]. Mitochondrial DNA is known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear DNA pseudogenes of the mtDNA. We present here the sequences of selected NUMTs, in which time of integration can be determined with sufficient precision. We report their chromosomal positions , their position within the great ape mtDNA phylogeny, and their times of integration into the nuclear genome...
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28698968/inhibition-of-poly-adp-ribose-polymerase-1-enhances-gene-expression-of-selected-sirtuins-and-app-cleaving-enzymes-in-amyloid-beta-cytotoxicity
#15
Przemysław L Wencel, Walter J Lukiw, Joanna B Strosznajder, Robert Piotr Strosznajder
Poly(ADP-ribose) polymerases (PARPs) and sirtuins (SIRTs) are involved in the regulation of cell metabolism, transcription, and DNA repair. Alterations of these enzymes may play a crucial role in Alzheimer's disease (AD). Our previous results indicated that amyloid beta (Aβ) peptides and inflammation led to activation of PARP1 and cell death. This study focused on a role of PARP1 in the regulation of gene expression for SIRTs and beta-amyloid precursor protein (βAPP) cleaving enzymes under Aβ42 oligomers (AβO) toxicity in pheochromocytoma cells (PC12) in culture...
July 12, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28694208/single-nucleotide-polymorphisms-minisequencing-in-hypervariable-regions-for-screening-of-thais
#16
Punlop Thongngam, Worraanong Leewattanapasuk, Tanin Bhoopat, Padchanee Sangthong
Mitochondrial DNA (mtDNA) analysis has displayed an important role and been considered as a powerful tool in various fields of forensic science applications. Nowadays, single nucleotide polymorphisms (SNPs) on mtDNA have become additional DNA markers when conventional STR typing practically fails. mtDNA sequencing of polymerase chain reaction (PCR) products from the hypervariable region I (HVRI) and II (HVRII) is the standard method of mtDNA analysis. However, mtDNA sequencing is rather expensive, time consuming and technically complex...
July 7, 2017: Gene
https://www.readbyqxmd.com/read/28693754/a-comprehensive-analysis-of-mitochondrial-genes-variants-and-their-association-with-antipsychotic-induced-weight-gain
#17
Kirti Mittal, Vanessa F Gonçalves, Ricardo Harripaul, Ari B Cuperfain, Brandi Rollins, Arun K Tiwari, Clement C Zai, Malgorzata Maciukiewicz, Daniel J Müller, Marquis P Vawter, James L Kennedy
Antipsychotic Induced Weight Gain (AIWG) is a common and severe side effect of many antipsychotic medications. Mitochondria play a vital role for whole-body energy homeostasis and there is increasing evidence that antipsychotics modulate mitochondrial function. This study aimed to examine the role of variants in nuclear-encoded mitochondrial genes and the mitochondrial DNA (mtDNA) in conferring risk for AIWG. We selected 168 European-Caucasian individuals from the CATIE sample based upon meeting criteria of multiple weight measures while taking selected antipsychotics (risperidone, quetiapine or olanzapine)...
July 7, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28690801/single-nucleotide-polymorphism-barcoding-of-cytochrome-c-oxidase-i-sequences-for-discriminating-17-species-of-columbidae-by-decision-tree-algorithm
#18
Cheng-Hong Yang, Kuo-Chuan Wu, Hans-Uwe Dahms, Li-Yeh Chuang, Hsueh-Wei Chang
DNA barcodes are widely used in taxonomy, systematics, species identification, food safety, and forensic science. Most of the conventional DNA barcode sequences contain the whole information of a given barcoding gene. Most of the sequence information does not vary and is uninformative for a given group of taxa within a monophylum. We suggest here a method that reduces the amount of noninformative nucleotides in a given barcoding sequence of a major taxon, like the prokaryotes, or eukaryotic animals, plants, or fungi...
July 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28665992/gene-expression-allelic-imbalance-in-ovine-brown-adipose-tissue-impacts-energy-homeostasis
#19
Shila Ghazanfar, Tony Vuocolo, Janna L Morrison, Lisa M Nicholas, Isabella C McMillen, Jean Y H Yang, Michael J Buckley, Ross L Tellam
Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects...
2017: PloS One
https://www.readbyqxmd.com/read/28663334/mitochondrial-genomic-backgrounds-affect-nuclear-dna-methylation-and-gene-expression
#20
Carolyn J Vivian, Amanda E Brinker, Stefan Graw, Devin C Koestler, Christophe Legendre, Gerald C Gooden, Bodour Salhia, Danny R Welch
Mitochondrial DNA (mtDNA) mutations and polymorphisms contribute to many complex diseases, including cancer. Using a unique mouse model that contains nuclear DNA (nDNA) from one mouse strain and homoplasmic mitochondrial haplotypes from different mouse strain(s) - designated Mitochondrial Nuclear Exchange (MNX) - we show that mtDNA can alter mammary tumor metastasis. Since retrograde and anterograde communication exist between the nuclear and mitochondrial genomes, we hypothesized that there are differential mtDNA-driven changes in nDNA expression and DNA methylation...
June 29, 2017: Cancer Research
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