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Oxidative stress cancer

Takeshi Yokoyama, Ryota Kitakami, Mineyuki Mizuguchi
MutT homologue 1 (MTH1) protects the nucleotide pool from oxidative stress by hydrolyzing oxidized nucleoside triphosphates and prevents their incorporation into DNA. Cancer cells are dependent on the MTH1 activity for survival due to the high-level of reactive oxygen species in cancer cells; therefore, MTH1 is considered to be a novel target for treatment of various cancers. Here, we show by X-ray crystallographic screening using an in-house cocktail library that α-mangostin, a natural xanthone from mangosteen pericarp, binds to the active site of MTH1...
February 7, 2019: European Journal of Medicinal Chemistry
Teresa Druck, Douglas G Cheung, Dongju Park, Francesco Trapasso, Flavia Pichiorri, Marco Gaspari, Tiziana Palumbo, Rami I Aqeilan, Eugenio Gaudio, Hiroshi Okumura, Rodolfo Iuliano, Cinzia Raso, Kari Green, Kay Huebner, Carlo M Croce
Fhit protein is lost in cancers of most, perhaps all, cancer types; when restored, it can induce apoptosis and suppress tumorigenicity, as shown in vitro and in mouse tumor models in vivo. Following protein cross-linking and proteomics analyses, we characterized a Fhit protein complex involved in triggering Fhit-mediated apoptosis. The complex includes the heat-shock chaperonin pair, HSP60/10, which is likely involved in importing Fhit into the mitochondria, where it interacts with ferredoxin reductase, responsible for transferring electrons from NADPH to cytochrome P450 via ferredoxin, in electron transport chain complex III...
February 15, 2019: Cell Death & Disease
Parvaneh Seiri, Abbas Abi, Mohammad Soukhtanloo
Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily. PPARs are categorized into three subtypes, PPARα, β/δ, and γ, encoded by different genes, expressed in diverse tissues and participate in various biological functions and can be activated by their metabolic derivatives in the body or dietary fatty acids. The PPAR-γ also takes parts in the regulation of energy balance, lipoprotein metabolism, insulin sensitivity, oxidative stress, and inflammatory signaling. It has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancers...
February 15, 2019: Journal of Cellular Biochemistry
Hsiaoju S Lee, Austin R Pantel, Rong Zhou, David A Mankoff
[18 F]FSPG was shown to provide an indirect measure of the cellular redox state and may be used as an early indicator of therapy response to cancer therapies that cause oxidative stress. A somewhat paradoxical finding was that reduced [18 F]FSPG cellular uptake was associated with either lower cellular concentrations of cystine or glutamate, despite opposing the transport of these substances in the Xc- antiporter, for which [18 F]FSPG is also a substrate. Further studies of the kinetics of [18 F]FSPG will help elucidate the factors mediating a decline in [18 F]FSPG with oxidative stress...
February 15, 2019: Cancer Research
Abinaya Manivannan, Jin-Hee Kim, Do-Sun Kim, Eun-Su Lee, Hye-Eun Lee
Raphanus sativus (Radish) belongs to the Brassicaceae family and is a widely consumed root vegetable all around the world. The nutritional and medicinal values of radishes have been proven by several researches. Extracts prepared from the aerial and underground parts of radishes have been used in the treatment of stomach disorders, urinary infections, hepatic inflammation, cardiac disorders and ulcers in folk medicine since the ancient times. The pharmaceutical potential of radishes is attributed to the presence of its beneficial secondary metabolites, such as glucosinolates, polyphenols and isothiocyanates...
February 14, 2019: Nutrients
Daniel Munro, Cécile Baldy, Matthew E Pamenter, Jason R Treberg
Naked mole-rats (NMRs) are mouse-sized mammals that exhibit an exceptionally long lifespan (>30 vs. <4 years for mice), and resist aging-related pathologies such as cardiovascular and pulmonary diseases, cancer, and neurodegeneration. However, the mechanisms underlying this exceptional longevity and disease resistance remain poorly understood. The oxidative stress theory of aging posits that (a) senescence results from the accumulation of oxidative damage inflicted by reactive oxygen species (ROS) of mitochondrial origin, and (b) mitochondria of long-lived species produce less ROS than do mitochondria of short-lived species...
February 15, 2019: Aging Cell
Steffen Daum, Johannes Toms, Viktor Reshetnikov, Gizem Hülya, Frank Hampel, Simone Maschauer, Amir H Hakimioun, Frank R Beierlein, Olaf Prante, Andriy Mokhir, Leopold Sellner, Michael Schmitt
N-Alkylaminoferrocene (NAAF)-based prodrugs are activated in the presence of elevated amounts of reactive oxygen species (ROS), that corresponds to cancer specific conditions, with formation of NAAF and p-quinone methide. These both products act synergistically by increasing oxidative stress in cancer cells that causes their death. Though it has been already demonstrated that the best prodrugs of this type retain their antitumor activity in vivo, the effects were found to be substantially weaker than those observed in cell cultures...
February 15, 2019: Bioconjugate Chemistry
James E Klaunig
BACKGROUND: Cancer is a major cause death in the worldwide. The etiology of cancer is linked environmental and genetic inheritance causes. Approximately 90 percent of all human cancers have an environmental cause (non-genetic inheritance) predominantly through lifestyle choices (smoking, diet, UV radiation) with the remainder infections and chemical exposure. Cancer is a multistage process that involves mutational changes and uncontrolled cell proliferation. Research has firmly established a causal and contributory role of oxidative stress and oxidative damage in cancer initiation and progression...
February 15, 2019: Current Pharmaceutical Design
Yiying Bian, Keunyoung Kim, Thien Ngo, Inho Kim, Ok-Nam Bae, Kyung-Min Lim, Jin-Ho Chung
BACKGROUND: Silver nanoparticles (AgNP) are widely used in medical practices owing to their distinct antibacterial, antiviral and anticancer activities. However, with increasing use of AgNP, concerns over its potential toxicity are also escalating. Here, we demonstrated the potential thrombotic effect of AgNP which was mediated by the procoagulant activity of red blood cells (RBCs). RESULTS: In freshly isolated human RBCs, AgNP, but not silver microparticles (AgMP), elicited morphological changes, phosphatidylserine (PS) exposure and microvesicles (MV) generation, the key indicators of procoagulant activity in RBCs at concentration ranges (≤ 100 μg/mL) that were free of significant hemolysis...
February 14, 2019: Particle and Fibre Toxicology
Vahid Reza Askari, Vafa Baradaran Rahimi, Amin Assaran, Mehrdad Iranshahi, Mohammad Hossein Boskabady
Inflammation is defined as a defensive response of the body against either the endogenous or exogenous triggers, while this process becomes chronic leading to various disorders such as asthma, cancers, and multiple sclerosis. Recently, pharmacological properties of different constituents of F. szowitsiana have been reported. In the present study, we aimed to evaluate the anti-oxidative and anti-inflammatory effects of the methanolic extract of F. szowitsiana root on human isolated lymphocytes. The effects of either F...
February 14, 2019: Drug and Chemical Toxicology
Alfredo Cruz-Gregorio, Imelda Martínez-Ramírez, José Pedraza-Chaverri, Marcela Lizano
Head and neck cancer (HNC) is the sixth cause of cancer-related death worldwide. Head and neck squamous cells carcinoma (HNSCC) is the most frequent subtype of HNC. The development of HNSCC is associated to alcohol consumption, smoking or infection by high-risk human Papillomavirus (HR-HPV). Although the incidence of cancers associated with alcohol and tobacco has diminished, HNSCC associated with HR-HPV has significantly increased in recent years. However, HPV-positive HNSCC responds well to treatment, which includes surgery followed by radiation or chemoradiation therapy...
February 5, 2019: Cancers
Anna Kurpińska, Joanna Suraj, Emilia Bonar, Agnieszka Zakrzewska, Marta Stojak, Magdalena Sternak, Agnieszka Jasztal, Maria Walczak
INTRODUCTION: The tumor-promoting rearrangement of the lungs facilitates the process of cancer cell survival in a foreign microenvironment and enables their protection against immune defense. The study aimed to define the fingerprint of the early rearrangement of the lungs via the proteomic profiling of the lung tissue in the experimental model of tumor metastasis in a murine 4 T1 mammary adenocarcinoma. MATERIALS AND METHODS: The studies were performed on 7-8-week-old BALB/c female mice...
February 11, 2019: Experimental and Molecular Pathology
Wafaa Al Tameemi, Tina P Dale, Rakad M Kh Al-Jumaily, Nicholas R Forsyth
While oxygen is critical to the continued existence of complex organisms, extreme levels of oxygen within a system, known as hypoxia (low levels of oxygen) and hyperoxia (excessive levels of oxygen), potentially promote stress within a defined biological environment. The consequences of tissue hypoxia, a result of a defective oxygen supply, vary in response to the gravity, extent and environment of the malfunction. Persistent pathological hypoxia is incompatible with normal biological functions, and as a result, multicellular organisms have been compelled to develop both organism-wide and cellular-level hypoxia solutions...
2019: Frontiers in Cell and Developmental Biology
Javier Garcia-Bermudez, Lou Baudrier, Erol Can Bayraktar, Yihui Shen, Konnor La, Rohiverth Guarecuco, Burcu Yucel, Danilo Fiore, Bernardo Tavora, Elizaveta Freinkman, Sze Ham Chan, Caroline Lewis, Wei Min, Giorgio Inghirami, David M Sabatini, Kıvanç Birsoy
Cholesterol is essential for cells to grow and proliferate. Normal mammalian cells meet their need for cholesterol through its uptake or de novo synthesis1 , but the extent to which cancer cells rely on each of these pathways remains poorly understood. Here, using a competitive proliferation assay on a pooled collection of DNA-barcoded cell lines, we identify a subset of cancer cells that is auxotrophic for cholesterol and thus highly dependent on its uptake. Through metabolic gene expression analysis, we pinpoint the loss of squalene monooxygenase expression as a cause of cholesterol auxotrophy, particularly in ALK+ anaplastic large cell lymphoma (ALCL) cell lines and primary tumours...
February 13, 2019: Nature
Jun Wang, Qi Wu, Jianxin Qiu
Clear cell renal cell carcinoma (ccRCC) is characterized by the activation of hypoxia-inducible factors and enhanced aerobic glycolysis. In our previous study, metabolic profiling revealed a threefold increase of fructose 1,6-bisphosphate (FBP) in ccRCC tissue compared with normal kidney tissue. As an important intermediate metabolite, its role in cancer development remains unknown. We found that high levels of FBP were required for cancer growth because of its ability to affect the redox status. Mechanistically, FBP regulated the redox status partially by suppressing NADPH oxidase isoform NOX4 activity in ccRCC cells...
February 13, 2019: Laboratory Investigation; a Journal of Technical Methods and Pathology
Erica W Cloer, Dennis Goldfarb, Travis P Schrank, Bernard E Weissman, Michael B Major
The Cancer Genome Atlas catalogued alterations in the Kelch-like ECH-associated protein 1 and nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway in 6.3% of patient samples across 226 studies, with significant enrichment in lung and upper airway cancers. These alterations constitutively activate NRF2-dependent gene transcription to promote many of the cancer hallmarks, including cellular resistance to oxidative stress, xenobiotic efflux, proliferation, and metabolic reprogramming. Almost universally, NRF2 activity strongly associates with poor patient prognosis and chemo- and radioresistance...
February 13, 2019: Cancer Research
Xiao Han, Junmin Zhang, Danfeng Shi, Yueting Wu, Ruijuan Liu, Tianyu Liu, Jianqiang Xu, Xiaojun Yao, Jianguo Fang
Ibrutinib (IBT), the first-in-class inhibitor of Bruton's tyrosine kinase (BTK), has demonstrated clinical activity against various B-cell malignancies. IBT is the second agent approved by U.S. Food and Drug Administration via Breakthrough Therapy Designation. Aside from its therapeutic mechanism through BTK inhibition, IBT has other target sites reported for cancer therapy, leading us to investigate whether IBT has unreported targets. Our study revealed that IBT can inhibit the growth of SMMC-7721 cells through irreversible inhibition of mammalian thioredoxin reductase (TrxR) enzymes, which are components of the thioredoxin (Trx) system...
February 13, 2019: Journal of Pharmacology and Experimental Therapeutics
Alexandra J White, Clarice R Weinberg, Ellen S O'Meara, Dale P Sandler, Brian L Sprague
BACKGROUND: Breast density is strongly related to breast cancer. Identifying associations between environmental exposures and density may elucidate relationships with breast cancer. Metals and polycyclic aromatic hydrocarbons (PAHs) may influence breast density via oxidative stress or endocrine disruption. METHODS: Study participants (n = 222,581) underwent a screening mammogram in 2011 at a radiology facility in the Breast Cancer Surveillance Consortium. Zip code residential levels of airborne PAHs and metals (arsenic, cadmium, chromium, cobalt, lead, manganese, mercury, nickel, and selenium) were assessed using the 2011 EPA National Air Toxics Assessment...
February 13, 2019: Breast Cancer Research: BCR
Jingwei Li, Xiaofei Liu, Hongzhi Chen, Ziyuan Sun, Hanhan Chen, Lei Wang, Xiaohui Sun, Xiangqi Li
BACKGROUND: Development of safe and effective chemopreventive agents is a winning strategy in reducing the morbidity and mortality of breast cancer. The current study was to investigate the mechanism-based chemopreventive potential of a Chinese herb formula Yanghe Huayan (YHHY) Decoction on the classical 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinogenesis model. METHODS: Female Sprague-Dawley rats at 42 days of age were orally administered with a human equivalent dose of YHHY Decoction at 0...
February 13, 2019: BMC Complementary and Alternative Medicine
Marta M Jankowska, Dorothy D Sears, Loki Natarajan, Elena Martinez, Cheryl A M Anderson, James F Sallis, Stephen A Matthews, Katie Crist, Lindsay Dillon, Eileen Johnson, Angelica Barrera-Ng, Kelsey Full, Suneeta Godbole, Jacqueline Kerr
BACKGROUND: Physical inactivity and unhealthy diet are modifiable behaviors that lead to several cancers. Biologically, these behaviors are linked to cancer through obesity-related insulin resistance, inflammation, and oxidative stress. Individual strategies to change physical activity and diet are often short lived with limited effects. Interventions are expected to be more successful when guided by multi-level frameworks that include environmental components for supporting lifestyle changes...
February 13, 2019: BMC Public Health
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