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https://www.readbyqxmd.com/read/28528001/a-lentinus-edodes-polysaccharide-induces-mitochondrial-mediated-apoptosis-in-human-cervical-carcinoma-hela-cells
#1
Guowei Ya
In this study, a homogeneous polysaccharide (LEP1) with an average molecular weight of 53kDa was successfully purified from the fruiting bodies of Lentinus edodes and its anticancer efficacy on human cervical carcinoma HeLa cells in vitro and associated possible molecular mechanism were also evaluated. MTT assay showed that LEP1 exhibited a dose-dependent inhibitory effect on the proliferation of HeLa cells and caused apoptotic death. Our present findings provided the first evidence that LEP1 induced the apoptosis of HeLa cells via a mitochondria dependent pathway, as indicated by an increase in Bax/Bcl-2 ratio, a loss of mitochondrial membrane potential (Δym), the release of cytochrome c from the mitochondria to the cytosol, activation of caspase-9 and caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP) in HeLa cells...
May 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28525742/ubiquitin-modification-by-the-e3-ligase-adp-ribosyltransferase-dtx3l-parp9
#2
Chun-Song Yang, Kasey Jividen, Adam Spencer, Natalia Dworak, Li Ni, Luke T Oostdyk, Mandovi Chatterjee, Beata Kuśmider, Brian Reon, Mahmut Parlak, Vera Gorbunova, Tarek Abbas, Erin Jeffery, Nicholas E Sherman, Bryce M Paschal
ADP-ribosylation of proteins is emerging as an important regulatory mechanism. Depending on the family member, ADP-ribosyltransferases either conjugate a single ADP-ribose to a target or generate ADP-ribose chains. Here we characterize Parp9, a mono-ADP-ribosyltransferase reported to be enzymatically inactive. Parp9 undergoes heterodimerization with Dtx3L, a histone E3 ligase involved in DNA damage repair. We show that the Dtx3L/Parp9 heterodimer mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin, exclusively in the context of ubiquitin processing by E1 and E2 enzymes...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525621/ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#3
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28523907/unexpected-position-dependent-effects-of-ribose-g-quartets-in-g-quadruplexes
#4
Jun Zhou, Samir Amrane, Frédéric Rosu, Gilmar F Salgado, Yunqiang Bian, Hisae Tateishi-Karimata, Eric Largy, Dursun Nizam Korkut, Anne Bourdoncle, Daisuke Miyoshi, Jian Zhang, Huangxian Ju, Wei Wang, Naoki Sugimoto, Valérie Gabelica, Jean-Louis Mergny
To understand the role of ribose G-quartets and how they affect the properties of G-quadruplex structures, we studied three systems in which one, two, three, or four deoxyribose G-quartets were substituted with ribose G-quartets. These systems were a parallel DNA intramolecular G-quadruplex d(TTGGGTGGGTTGGGTGGGTT) and two tetramolecular G-quadruplexes d(TGGGT) and d(TGGGGT). Thermal denaturation experiments revealed that ribose G-quartets have position-dependent and cumulative effects on G-quadruplex stability...
May 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28521469/licochalcone-e-induces-caspase-dependent-death-of-human-pharyngeal-squamous-carcinoma-cells-through-the-extrinsic-and-intrinsic-apoptotic-signaling-pathways
#5
Sang-Joun Yu, In-A Cho, Kyeong-Rok Kang, Yi-Ra Jung, Seung Sik Cho, Goo Yoon, Ji-Su Oh, Jae-Seek You, Yo-Seob Seo, Gyeong-Je Lee, Sook-Young Lee, Do Kyung Kim, Chun Sung Kim, Su-Gwan Kim, Mi-Ae Jeong, Jae-Sung Kim
The aim of the present study was to investigate licochalcone-E (Lico-E)-induced apoptosis and the associated apoptotic signaling pathway in FaDu cells, a human pharyngeal squamous carcinoma cell line. Treatment with Lico-E exhibited significant cytotoxicity on FaDu cells in a concentration-dependent manner. The IC50 value of Lico-E in FaDu cells was ~50 µM. Treatment with Lico-E increased the number of dead FaDu cells. Furthermore, chromatin condensation, which is associated with apoptotic cell death, was observed in FaDu cells treated with Lico-E for 24 h...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28518408/s-adenosylmethionine-mediated-apoptosis-is-potentiated-by-autophagy-inhibition-induced-by-chloroquine-in-human-breast-cancer-cells
#6
Donatella Delle Cave, Vincenzo Desiderio, Laura Mosca, Concetta Paola Ilisso, Luigi Mele, Michele Caraglia, Giovanna Cacciapuoti, Marina Porcelli
The naturally-occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28515263/ligand-induced-activation-of-human-trpm2-requires-the-terminal-ribose-of-adpr-and-involves-arg-1433-and-tyr-1349
#7
Ralf Fliegert, Joanna M Watt, Anja Schöbel, Monika D Rozewitz, Christelle Moreau, Tanja Kirchberger, Mark P Thomas, Wiebke Sick, Andrea C Araujo, Angelika Harneit, Barry Vl Potter, Andreas H Guse
TRPM2 is a Ca(2+)-permeable non-selective cation channel activated by binding of adenosine 5'-diphosphoribose (ADPR) to its cytoplasmic NUDT9H domain. Activation of TRPM2 by ADPR downstream of oxidative stress has been implicated in the pathogenesis of a number of human diseases rendering TRPM2 an attractive novel target for pharmacological intervention. However, the structural basis underlying this activation is largely unknown. Since ADP alone did not activate or antagonize the channel, we used a chemical biology approach employing synthetic analogues to focus on the role of the ADPR terminal ribose...
May 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28515157/carboxyamidotriazole-synergizes-with-sorafenib-to-combat-non-small-cell-lung-cancer-through-inhibition-of-nanog-and-aggravation-of-apoptosis
#8
Chen Chen, Rui Ju, Jing Shi, Wei Chen, Fangrui Sun, Lei Zhu, Juan Li, Dechang Zhang, Caiying Ye, Lei Guo
Lung cancer is the leading cause of cancer-related deaths in the world. In this study, we investigated the combination of carboxyamidotriazole (CAI) and sorafenib in NSCLC in vitro and in vivo, to test whether CAI enhances the antitumor effects of sorafenib and reduces its side effects. The combination index (CI) showed that co-administration of CAI and sorafenib synergistically inhibited the proliferation of NSCLC cells (Lewis lung carcinoma, A549, NCI-H1975). The cell death led by the treatment of combination drugs was attributed to apoptosis which was accompanied with activation of caspase 3 and poly ADP-ribose polymerase...
May 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28515149/pyruvate-kinase-inhibits-proliferation-during-postnatal-cerebellar-neurogenesis-and-suppresses-medulloblastoma-formation
#9
Katherine Tech, Andrey P Tikunov, Hamza Farooq, A Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C Green, Hedi Liu, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven Jm Jones, Marco A Marra, Matthew G Vander Heiden, Michael D Taylor, Jeffrey MacDonald, Timothy R Gershon
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNPs), and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of Hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting Pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation and tumorigenesis...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28514905/evodiamine-prevents-glioma-growth-induces-glioblastoma-cell-apoptosis-and-cell-cycle-arrest-through-jnk-activation
#10
Wen-Shin Wu, Chih-Chiang Chien, Kao-Hui Liu, Yen-Chou Chen, Wen-Ta Chiu
Evodiamine (EVO) is an active medicinal compound derived from the traditional herbal medicine Evodia rutaecarpa. It has been reported that evodiamine has several beneficial biological properties, including anticancer and anti-inflammatory activities. However, the in vitro and in vivo anticancer activities of EVO against the growth of glioblastoma cells remain undefined. EVO induced significant decreases in the viability of U87 and C6 glioma cells, but not of primary astrocytes, according with the occurrence of apoptotic characteristics including DNA ladders, caspase-3 and poly(ADP ribose) polymerase (PARP) protein cleavage, and hypodiploid cells...
May 18, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28514875/identification-of-novel-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-using-computational-approaches
#11
Manish Kesherwani, Sriram Raghavan, Krishnasamy Gunasekaran, Devadasan Velmurugan
Nicotinamide Phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the biosynthesis of NAD. Cancer cells have elevated poly [ADP-Ribose] polymerase 1 (PARP) activity as well as the immense necessity of ATP: thereby consuming NAD at a higher rate than normal tissues. The perturbation of these intracellular processes is more sensitive and highly dependent on NAMPT to maintain the required NAD levels. Functional inhibition of NAMPT is, therefore, a promising drug target in therapeutic oncology. In this study, the importance of intermolecular contacts was realized based on contact occupancy and favorable energetic from molecular dynamic simulation to discern non-critical contacts of four different classes of potential NAMPT inhibitor bound complexes...
May 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28514652/thymidine-catabolism-as-a-metabolic-strategy-for-cancer-survival
#12
Sho Tabata, Masatatsu Yamamoto, Hisatsugu Goto, Akiyoshi Hirayama, Maki Ohishi, Takuya Kuramoto, Atsushi Mitsuhashi, Ryuji Ikeda, Misako Haraguchi, Kohichi Kawahara, Yoshinari Shinsato, Kentaro Minami, Atsuro Saijo, Masaki Hanibuchi, Yasuhiko Nishioka, Saburo Sone, Hiroyasu Esumi, Masaru Tomita, Tomoyoshi Soga, Tatsuhiko Furukawa, Shin-Ichi Akiyama
Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28511952/lithium-ameliorates-lipopolysaccharide-induced-neurotoxicity-in-the-cortex-and-hippocampus-of-the-adult-rat-brain
#13
Muhammad Sohail Khan, Tahir Ali, Muhammad Noman Abid, Myeung Hoon Jo, Amjad Khan, Min Woo Kim, Gwang Ho Yoon, Eun Woo Cheon, Shafiq Ur Rehman, Myeong Ok Kim
Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α)...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28510338/therapeutic-targeting-of-poly-adp-ribose-polymerase-1-in-cancer-current-developments-therapeutic-strategies-and-future-opportunities
#14
REVIEW
Jyotika Rajawat, Nidhi Shukla, Durga Prasad Mishra
Poly(ADP-ribose) polymerase-1 (PARP1) is key protein involved in numerous cellular processes including DNA repair, replication, and transcription. PARP interacts directly, indirectly, or via PARylation with various oncogenic proteins and regulates several transcription factors, thereby modulating carcinogenesis. Therapeutic inhibition of PARP is therefore perceived as a promising anticancer strategy, and a number of PARP inhibitors (PARPi) are in different stages of clinical evaluation. PARPi inhibit the DNA repair pathway and thus form the concept of synthetic lethality in cancer therapeutics...
May 16, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28508305/recent-advances-in-targeting-dna-repair-pathways-for-the-treatment-of-ovarian-cancer-and-their-clinical-relevance
#15
REVIEW
Katsutoshi Oda, Michihiro Tanikawa, Kenbun Sone, Mayuyo Mori-Uchino, Yutaka Osuga, Tomoyuki Fujii
Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as one of the major molecular-targeted therapeutics for inhibiting DNA damage response. The PARP inhibitor, olaparib, has been clinically applied for treating certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and the United States. It was also designated on 24 March 2017 as an orphan drug in Japan for similar clinical indications. In this review, we discuss (i) the prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and ovarian cancer patients, and (iv) non-BRCA genes that may be associated with homologous recombination deficiency...
May 15, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28507315/the-herpesvirus-nuclear-egress-complex-component-ul31-can-be-recruited-to-sites-of-dna-damage-through-poly-adp-ribose-binding
#16
Maxwell R Sherry, Thomas J M Hay, Michael A Gulak, Arash Nassiri, Renée L Finnen, Bruce W Banfield
The herpes simplex virus (HSV) UL31 gene encodes a conserved member of the herpesvirus nuclear egress complex that not only functions in the egress of DNA containing capsids from the nucleus, but is also required for optimal replication of viral DNA and its packaging into capsids. Here we report that the UL31 protein from HSV-2 can be recruited to sites of DNA damage by sequences found in its N-terminus. The N-terminus of UL31 contains sequences resembling a poly (ADP-ribose) (PAR) binding motif suggesting that PAR interactions might mediate UL31 recruitment to damaged DNA...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28504908/mammea-longifolia-planch-and-triana-fruit-extract-induces-cell-death-in-the-human-colon-cancer-cell-line-sw480-via-mitochondria-related-apoptosis-and-activation-of-p53
#17
Chunmei Li, Yoonhwa Jeong, Misook Kim
The methanol extract of Mammea longifolia Planch. and Triana (M. longifolia) fruit was studied for anticancer and apoptotic effects in the SW480 colon cancer cell line. The apoptotic and necrotic effects of M. longifolia were detected by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) and lactate dehydrogenase assays, respectively. One hundred μg/mL of the extract killed ∼82.4% of the cells; however, 2% of the death was related to necrosis. The morphological changes in M. longifolia-stimulated SW480 cells were observed directly by light microscopy...
May 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28504680/nm-seq-maps-2-o-methylation-sites-in-human-mrna-with-base-precision
#18
Qing Dai, Sharon Moshitch-Moshkovitz, Dali Han, Nitzan Kol, Ninette Amariglio, Gideon Rechavi, Dan Dominissini, Chuan He
The ribose of RNA nucleotides can be 2'-O-methylated (Nm). Despite advances in high-throughput detection, the inert chemical nature of Nm still limits sensitivity and precludes mapping in mRNA. We leveraged the differential reactivity of 2'-O-methylated and 2'-hydroxylated nucleosides to periodate oxidation to develop Nm-seq, a sensitive method for transcriptome-wide mapping of Nm with base precision. Nm-seq uncovered thousands of Nm sites in human mRNA with features suggesting functional roles.
May 15, 2017: Nature Methods
https://www.readbyqxmd.com/read/28503382/poly-adp-ribosylation-is-present-in-murine-sciatic-nerve-fibers-and-is-altered-in-a-charcot-marie-tooth-1e-neurodegenerative-model
#19
Laura I Lafon Hughes, Carlos J Romeo Cardeillac, Karina B Cal Castillo, Salomé C Vilchez Larrea, José R Sotelo Sosa, Gustavo A Folle Ungo, Silvia H Fernández Villamil, Alejandra E Kun González
BACKGROUND: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28502297/-knock-down-of-cadherin-17-inhibits-proliferation-and-promote-apoptosis-in-noscapine-resistant-human-sw480-colon-cancer-cells
#20
Zheng Han, Xiaodong Huang, Meng Liu, Jie Tan, Qingxi Zhu, Yanfen Wang, Yishan Cai, Aifang Chen, Xia Tian
Objective To investigate the effects of cadherin 17 (CDH17) on the proliferation and apoptosis of noscapine-resistant human SW480 colon cancer cells. Methods The level of CDH17 in noscapine-resistant human SW480 colon cancer cells was knocked down by small interfering RNA (siRNA), and the silence was confirmed by Western blotting and real-time quantitative PCR. Transfected SW480 cells were treated with noscapine, and then the proliferation and cell viability of SW480 cells were measured by MTT assay and plate clone formation assay, respectively; the apoptosis of SW480 cells was detected by flow cytometry combined with annexinV-FITC/PI staining; the expressions of poly-ADP-ribose polymerase (PARP) and caspase-3 were determined by Western blotting...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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