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https://www.readbyqxmd.com/read/29220397/desethylamiodarone-a-metabolite-of-amiodarone-induces-apoptosis-on-t24-human-bladder-cancer-cells-via-multiple-pathways
#1
Zita Bognar, Katalin Fekete, Csenge Antus, Eniko Hocsak, Rita Bognar, Antal Tapodi, Arpad Boronkai, Nelli Farkas, Ferenc Gallyas, Balazs Sumegi, Arpad Szanto
Bladder cancer (BC) is a common malignancy of the urinary tract that has a higher frequency in men than in women. Cytostatic resistance and metastasis formation are significant risk factors in BC therapy; therefore, there is great interest in overcoming drug resistance and in initiating research for novel chemotherapeutic approaches. Here, we suggest that desethylamiodarone (DEA)-a metabolite of amiodarone-may have cytostatic potential. DEA activates the collapse of mitochondrial membrane potential (detected by JC-1 fluorescence), and induces cell death in T24 human transitional-cell bladder carcinoma cell line at physiologically achievable concentrations...
2017: PloS One
https://www.readbyqxmd.com/read/29216878/adaptive-phenotype-drives-resistance-to-androgen-deprivation-therapy-in-prostate-cancer
#2
Nicoletta Ferrari, Ilaria Granata, Matteo Capaia, Marina Piccirillo, Mario Rosario Guarracino, Roberta Venè, Antonella Brizzolara, Andrea Petretto, Elvira Inglese, Martina Morini, Simonetta Astigiano, Adriana Agnese Amaro, Francesco Boccardo, Cecilia Balbi, Paola Barboro
BACKGROUND: Prostate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges. METHODS: Western blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP...
December 8, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29205518/therapeutic-and-prognostic-significance-of-parp-1-in-advanced-mycosis-fungoides-and-sezary-syndrome
#3
David Lemchak, Swati Banerjee, Shaunak S Digambar, Brian L Hood, Thomas P Conrads, Jaroslav Jedrych, Larisa Geskin, Oleg E Akilov
While mycosis fungoides (MF) is typically an indolent malignancy, it may infrequently undertake an aggressive course. We used proteomic analyses to identify a biomarker of the aggressive course of MF. Results of this investigation demonstrated that PARP-1, heat shock protein family A (Hsp70) member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP-depending RNA-helicase (DDX17), and the α isoform of lamina-associated polypeptide 2 (TMPO) had higher expression in aggressive disease versus non-aggressive. Moreover, PARP-1 was overexpressed in patients with early stage of MF who developed later an aggressive disease...
December 5, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/29193605/dihydroxyacetone-induces-g2-m-arrest-and-apoptotic-cell-death-in-a375p-melanoma-cells
#4
Kelly R Smith, Molley Granberry, Marcus C B Tan, Casey L Daniel, Natalie R Gassman
The active ingredient in sunless tanning products (STPs) is a simple sugar, dihydroxyacetone (DHA). Several studies have demonstrated that DHA is absorbed within the viable layers of skin and not fully contained within the stratum corneum. Additionally, spray tanning and other aerosolized application methods have increased the risk of internal exposure through mucous membranes and inhalation. Beyond its presence in STPs, DHA also occurs as an endogenous by-product of fructose metabolism, and an excess of DHA in cells can induce advanced glycation end (AGE) products and oxidative stress...
November 29, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29187880/the-parp-1-inhibitor-olaparib-suppresses-brca1-protein-levels-increases-apoptosis-and-causes-radiation-hypersensitivity-in-brca1-lymphoblastoid-cells
#5
Emma C Bourton, Pia-Amata Ahorner, Piers N Plowman, Sheba Adam Zahir, Hussein Al-Ali, Christopher N Parris
The use of polyADPribose polymerase inhibitors in cancer treatment provides a unique opportunity to target DNA repair processes in cancer cells while leaving normal tissue intact. The PARP-1 enzyme repairs DNA single strand breaks (SSB). Therefore PARP-1 inhibition in BRCA1 negative cancers results in the formation of cytotoxic DNA double strand breaks (DSB) causing synthetic lethality. The use of PARP1 inhibitors is gaining momentum in the treatment of a variety of tumours with BRCA1 involvement including breast, ovarian, pancreatic and prostate cancer...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29184509/parp-1-variant-rs1136410-confers-protection-against-coronary-artery-disease-in-a-chinese-han-population-a-two-stage-case-control-study-involving-5643-subjects
#6
Xue-Bin Wang, Ning-Hua Cui, Shuai Zhang, Shu-Ren Guo, Ze-Jin Liu, Liang Ming
Inhibition of poly(ADP-ribose) polymerase (PARP) may protect against coronary artery disease (CAD) in animal models, and rs1136410, a non-synonymous single nucleotide polymorphism (SNP) in PARP-1, has a potential impact on PARP activities in vitro. This two-stage case-control study, involving 2803 CAD patients and 2840 controls, aimed to investigate the associations of PARP-1 rs1136410 with CAD development, lipid levels, PARP activities, 8-hydroxy-2'-dexyguanosine (8-OHdG), and interleukin (IL)-6 levels in a Chinese Han population...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29184090/thyroid-hormones-derivatives-reduce-proliferation-and-induce-cell-death-and-dna-damage-in-ovarian-cancer
#7
Elena Shinderman-Maman, Keren Cohen, Dotan Moskovich, Aleck Hercbergs, Haim Werner, Paul J Davis, Martin Ellis, Osnat Ashur-Fabian
Ovarian cancer is a highly aggressive disease and novel treatments are required. Thyroid hormones binding to αvβ3 integrin produced growth-promoting activities in ovarian cancer and we hypothesized that natural thyroid hormone derivatives may antagonize these actions. The effect of three antagonists, tetraiodoacetic acid (tetrac), triiodothyroacetic acid (triac) and 3-iodothyronamine (T1AM), on cell proliferation, cell death and DNA damage was studied in two ovarian cancer cell lines (OVCAR3 and A2780), normal hamster ovary control cells (CHOK1) and αvβ3-deficient or transfected HEK293 cells...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29182629/effects-of-peroxisome-proliferator-activated-receptors-ppar-%C3%AE-and-%C3%AE-agonists-on-cochlear-protection-from-oxidative-stress
#8
Marijana Sekulic-Jablanovic, Vesna Petkovic, Matthew B Wright, Krystsina Kucharava, Nathan Huerzeler, Soledad Levano, Yves Brand, Katharina Leitmeyer, Andrea Glutz, Alexander Bausch, Daniel Bodmer
Various insults cause ototoxicity in mammals by increasing oxidative stress leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs; e.g., pioglitazone) and fibrate (e.g., fenofibrate) drugs are used for the treatment of diabetes and dyslipidemia. These agents target the peroxisome proliferator-activated receptors, PPARγ and PPARα, which are transcription factors that influence glucose and lipid metabolism, inflammation, and organ protection. In this study, we explored the effects of pioglitazone and other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis in mouse organ of Corti (OC) explants...
2017: PloS One
https://www.readbyqxmd.com/read/29179487/parp-1-promotes-tumor-recurrence-after-warm-ischemic-liver-graft-transplantation-via-neutrophil-recruitment-and-polarization
#9
Shuai Wang, Fa-Ji Yang, Xun Wang, Yuan Zhou, Bo Dai, Bing Han, Hu-Cheng Ma, Yi-Tao Ding, Xiao-Lei Shi
Poly (ADP-ribose) polymerase 1 (PARP-1) is a crucial contributor to exacerbate ischemia and reperfusion (IR) injury and cancer process. However, there is little research into whether PARP-1 affects the hepatocellular carcinoma (HCC) recurrence after liver transplantation. In this study, we investigated the influence of PARP-1 on hepatic neutrophil mobilizing and phenotype shifting which may lead to HCC recurrence after liver transplantation. We found that rats received the grafts with warm ischemic injury had higher risk of HCC recurrence, which was markedly prevented by pharmacological inhibition of PARP-1 after liver transplantation...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29170981/natural-dietary-supplementation-of-anthocyanins-via-pi3k-akt-nrf2-ho-1-pathways-mitigate-oxidative-stress-neurodegeneration-and-memory-impairment-in-a-mouse-model-of-alzheimer-s-disease
#10
Tahir Ali, Taehyun Kim, Shafiq Ur Rehman, Muhammad Sohail Khan, Faiz Ul Amin, Mehtab Khan, Muhammad Ikram, Myeong Ok Kim
Well-established studies have shown an elevated level of reactive oxygen species (ROS) that induces oxidative stress in the Alzheimer's disease (AD) patient's brain and an animal model of AD. Herein, we investigated the underlying anti-oxidant neuroprotective mechanism of natural dietary supplementation of anthocyanins extracted from Korean black beans in the amyloid precursor protein/presenilin-1 (APP/PS1) mouse model of AD. Both in vivo (APP/PS1 mice) and in vitro (mouse hippocampal HT22 cells) results demonstrated that anthocyanins regulate the phosphorylated-phosphatidylinositol 3-kinase-Akt-glycogen synthase kinase 3 beta (p-PI3K/Akt/GSK3β) pathways and consequently attenuate amyloid beta oligomer (AβO)-induced elevations in ROS level and oxidative stress via stimulating the master endogenous anti-oxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (Nrf2/HO-1) pathways and prevent apoptosis and neurodegeneration by suppressing the apoptotic and neurodegenerative markers such as activation of caspase-3 and PARP-1 expression as well as the TUNEL and Fluoro-Jade B-positive neuronal cells in the APP/PS1 mice...
November 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29164711/vitamin-e-improves-testicular-damage-in-streptozocin-induced-diabetic-rats-via-increasing-vascular-endothelial-growth-factor-and-poly-adp-ribose-polymerase-1
#11
S S Omar, R G Aly, N M Badae
The precise mechanism by which diabetes impairs spermatogenesis and testicular function is not exactly known. Vascular endothelial growth factor (VEGF) and poly(ADP-ribose) polymerase-1 (PARP-1) are important for germ cell homeostasis and repair of DNA respectively. The aim of this study was to investigate the correlation between diabetes-induced testicular damage and testicular VEGF and PARP-1 expression and the possible protective role of vitamin E supplementation. A total of 45 male Wistar albino rats were randomly divided into three groups: Group I (nondiabetic rats), Group II (streptozocin-induced diabetic rats) and Group III (streptozocin-induced diabetic rats treated orally with 0...
November 21, 2017: Andrologia
https://www.readbyqxmd.com/read/29156828/the-%C3%AE-glucan-from-lentinus-edodes-suppresses-cell-proliferation-and-promotes-apoptosis-in-estrogen-receptor-positive-breast-cancers
#12
Hui Xu, Siwei Zou, Xiaojuan Xu
Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the β-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of ∼53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152107/neoadjuvant-olaparib-targets-hypoxia-to-improve-radioresponse-in-a-homologous-recombination-proficient-breast-cancer-model
#13
Gerben R Borst, Ramya Kumareswaran, Hatice Yücel, Seyda Telli, Trevor Do, Trevor McKee, Gaetano Zafarana, Jos Jonkers, Marcel Verheij, Mark J O'Connor, Sven Rottenberg, Robert G Bristow
Clinical trials are studying the benefits of combining the PARP-1 inhibitor olaparib with chemotherapy and radiotherapy treatment in a variety of cancer increasing the therapeutic ratio for olaparib may come from its ability to modify the tumour microenvironment by targeting homologous recombination-deficient, hypoxic tumour clonogens, and/or increasing tumour-associated vasodilation to improve oxygenation. Herein, we investigated the effect of prolonged neoadjuvant exposure to olaparib on the tumor microenvironment using a genetically-engineered mouse p53-/- syngeneic breast cancer model, which is proficient in homology-directed DNA repair...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149203/alc1-chd1l-a-chromatin-remodeling-enzyme-is-required-for-efficient-base-excision-repair
#14
Masataka Tsuda, Kosai Cho, Masato Ooka, Naoto Shimizu, Reiko Watanabe, Akira Yasui, Yuka Nakazawa, Tomoo Ogi, Hiroshi Harada, Keli Agama, Jun Nakamura, Ryuta Asada, Haruna Fujiike, Tetsushi Sakuma, Takashi Yamamoto, Junko Murai, Masahiro Hiraoka, Kaoru Koike, Yves Pommier, Shunichi Takeda, Kouji Hirota
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1's ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2...
2017: PloS One
https://www.readbyqxmd.com/read/29143372/a-critical-role-of-trpm2-channel-in-a%C3%AE-42-induced-microglial-activation-and-generation-of-tumor-necrosis-factor-%C3%AE
#15
Sharifah Alawieyah Syed Mortadza, Joan A Sim, Veronika E Neubrand, Lin-Hua Jiang
Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD...
November 16, 2017: Glia
https://www.readbyqxmd.com/read/29136949/minocycline-improves-cardiac-function-after-myocardial-infarction-in-rats-by-inhibiting-activation-of-parp-1
#16
Hua Zhao, Jianjun Zhang, Gang Hong
To investigate whether Minocycline can protect myocardial cells after myocardial infarction and improve myocardial remodeling through inhibiting PARP-1 activity, thus improving cardiac function. 50 male Wistar rats aged 4 months were used to establish the myocardial infarction model. The experimental rats underwent the echocardiography at 3d, 14d and 28d after operation. After 28days, the rats were executed and the myocardial tissues in the infarct-related zone were treated with immumohistochemical staining and molecular biology detection...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29134494/expression-of-telomere-associated-proteins-is-interdependent-to-stabilize-native-telomere-structure-and-telomere-dysfunction-by-g-quadruplex-ligand-causes-terra-upregulation
#17
Ratan Sadhukhan, Priyanka Chowdhury, Sourav Ghosh, Utpal Ghosh
Telomere DNA can form specialized nucleoprotein structure with telomere-associated proteins to hide free DNA ends or G-quadruplex structures under certain conditions especially in presence of G-quadruplex ligand. Telomere DNA is transcribed to form non-coding telomere repeat-containing RNA (TERRA) whose biogenesis and function is poorly understood. Our aim was to find the role of telomere-associated proteins and telomere structures in TERRA transcription. We silenced four [two shelterin (TRF1, TRF2) and two non-shelterin (PARP-1, SLX4)] telomere-associated genes using siRNA and verified depletion in protein level...
November 13, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29128369/inhibition-of-poly-adp-ribose-polymerase-1-alters-expression-of-mitochondria-related-genes-in-pc12-cells-relevance-to-mitochondrial-homeostasis-in-neurodegenerative-disorders
#18
Grzegorz A Czapski, Magdalena Cieślik, Przemysław L Wencel, Sylwia Wójtowicz, Robert P Strosznajder, Joanna B Strosznajder
Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29120085/novel-au-and-ag-carbene-complexes-exert-anti-tumor-effects-triggering-the-ros-dependent-intrinsic-apoptotic-pathway
#19
Domenico Iacopetta, Annaluisa Mariconda, Carmela Saturnino, Anna Caruso, Giuseppe Palma, Jessica Ceramella, Noemi Muià, Mariarita Perri, Maria Stefania Sinicropi, Maria Cristina Caroleo, Pasquale Longo
Cisplatin and other platinum-based drugs are well-known valid anticancer drugs. However, during the chemotherapy, the presence of numerous side effects and the onset of frequent phenomena of resistance pushes forward many research groups to devise new metal-based compounds holding improved anticancer properties and lower undesired effects. Amongst the variety of synthesized compounds, significant anti-proliferative effects were obtained employing organometallic compounds, particularly those based on silver or gold...
November 9, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29117515/metformin-and-epothilone-a-treatment-up-regulate-pro-apoptotic-parp-1-casp-3-and-h2ax-genes-and-decrease-of-akt-kinase-level-to-control-cell-death-of-human-hepatocellular-carcinoma-and-ovary-adenocarcinoma-cells
#20
Aneta Rogalska, Barbara Bukowska, Agnieszka Marczak
High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy. Here, we investigated genotoxic and pro-oxidant effects of metformin (MET) and epothilone A (A) in combination with respect to apoptosis in HepG2 and SKOV-3 cancer cells. Reactive oxygen species (ROS) was studied using 2',7'-dichlorodihydrofluoresein diacetate, and samples were analyzed for the presence and absence of the N-acetylcysteine (NAC). Expression of genes involved in programmed cell death, oxidative and alkylating DNA damage was measured...
November 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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