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Cancer AND NOX

Jiahao Zhang, Huachao Li, Qipeng Wu, Yueming Chen, Yanchao Deng, Zhicheng Yang, Luyong Zhang, Bing Liu
M2-type tumor-associated macrophages (TAMs) infiltration contributes to cancer malignant progression. However, the mechanisms for controlling recruitment and M2 polarization of macrophages by cancer cells are largely unclear. NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and mediates cancer progression. NOXs are in close relation with cancer-related inflammation, nevertheless, whether tumoral NOXs influence microenvironmental macrophages remains undentified. This study found that there was a close association between NOX4 expression and macrophage chemotaxis in patients with NSCLC analyzed using TCGA RNA-sequencing data...
February 6, 2019: Redox Biology
David Fulton, Xueyi Li, Zsuzsanna Bordan, Yusi Wang, Keyvan Mahboubi, Radu Daniel Rudic, Stephen Haigh, Feng Chen, Scott A Barman
SIGNIFICANCE: Pulmonary Arterial Hypertension (PAH) is a progressive disease arising from the narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular (RV) failure. A defining characteristic of PAH is the excessive and unrelenting inward remodeling of PA that includes increased proliferation, inflammation and fibrosis. CRITICAL ISSUES: There is no cure for PAH nor interventions that effectively arrest or reverse PA remodeling and intensive research over the past several decades has sought to identify novel molecular mechanisms of therapeutic value...
February 15, 2019: Antioxidants & Redox Signaling
Kanae Echizen, Keigo Horiuchi, Yayoi Aoki, Yoichi Yamada, Toshinari Minamoto, Hiroko Oshima, Masanobu Oshima
We previously showed that NADPH oxidase organizer 1 (Noxo1), a component of NADPH oxidase 1 (NOX1), is a TNF-α-induced tumor-promoting factor in gastric tumorigenesis. However, the mechanism of NOX1-induced reactive oxygen species (ROS) signaling for the gastric tumorigenesis has not been understood. Here, we showed that expression of NOX1 complex components, including Noxo1, but not other NOX family members was significantly upregulated in both mouse models for gastritis and gastric tumors, which was associated with increased ROS levels...
January 30, 2019: Oncogene
Nicholas W Eyrich, Chad R Potts, M Hope Robinson, Victor Maximov, Anna M Kenney
Cerebellar development is a highly regulated process involving numerous factors acting with high specificity, both temporally and by location. Part of this process involves extensive proliferation of cerebellar granule neuron precursors (CGNPs) induced by Sonic Hedgehog (SHH) signaling, but downstream effectors of mitogenic signaling are still being elucidated. Using primary CGNP cultures, a well-established model for SHH-driven proliferation, we show that SHH-treated CGNPs feature high levels of Hypoxia-Inducible Factor-1-Alpha (HIF1α), which is known to promote glycolysis, stemness, and angiogenesis...
January 28, 2019: Molecular and Cellular Biology
Jinseon Jeong, Yong-Jae Kim, Do Young Lee, Byoung-Gon Moon, Ki-Young Sohn, Sun Young Yoon, Jae Wha Kim
Cancer patients treated with chemotherapy often experience a rapid decline of blood neutrophils, a dose-limiting side effect called chemotherapy-induced neutropenia. This complication brings about dose reductions or cessation of chemotherapy during treatment of cancer patients because a rapid decline of neutrophil counts increases susceptibility to infection. Here, we found that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation via the inhibition of neutrophil-attracting chemokine production in macrophages using in vivo and in vitro approaches...
2019: Cell & Bioscience
Jing Liu, Haizhou Zhu, Gurdat Premnauth, Kaylin G Earnest, Patricia Hahn, George Gray, Jack A Queenan, Lisa E Prevette, Safnas F AbdulSalam, Ana Luisa Kadekaro, Edward J Merino
UV irradiation is a major driver of DNA damage and ultimately skin cancer. UV exposure leads to persistent radicals that generate ROS over prolonged periods of time. Toward the goal of developing long-lasting antioxidants that can penetrate skin, we have designed a ROS-initiated protective (RIP) reagent that, upon reaction with ROS (antioxidant activity), self-cyclizes and then releases the natural product apocynin. Apocynin is a known antioxidant and inhibitor of NOX oxidase enzymes. A key phenol on the compound 1 controls ROS-initiated cyclization and makes 1 responsive to ROS with a EC50 comparable to common antioxidants in an ABTS assay...
December 31, 2018: Free Radical Biology & Medicine
Cecilia Prata, Carlotta Facchini, Emanuela Leoncini, Monia Lenzi, Tullia Maraldi, Cristina Angeloni, Laura Zambonin, Silvana Hrelia, Diana Fiorentini
Sulforaphane, a biologically active isothiocyanate compound extracted from cruciferous vegetables, has been shown to exert cytotoxic effects on many human cancer cells, including leukemia. However, the exact molecular mechanisms behind the action of sulforaphane in hematological malignancies are still unclear. Like other cancer cells, leukemia cells produce high level of reactive oxygen species; in particular, hydrogen peroxide derived from Nox family is involved in various redox signal transduction pathways, promoting cell proliferation and survival...
2018: Oxidative Medicine and Cellular Longevity
Shizhen Dong, Menglu Chen, Faliang Dai, Qingxia Xuan, Pan Chen, Dandan Feng, Lei Gao, Chendi Zhu, Yongchao Chang, Fong-Fong Chu, Qiang Gao
AIM: This study investigated the impact of 5-hydroxytryptamine (5-HT) on the expression of NOXs in dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6J (B6) mice at 6 to 8 weeks of age were treated with 5-HT, DSS, or DSS + 5-HT. After 6-day treatment, the severity of colitis, infiltration of leukocytes, and messenger RNA (mRNA) and/or protein levels of Nox1, Nox2, Nox4, and Duox2 were analyzed in the colon by real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Western blot analysis...
December 7, 2018: Journal of Cellular Biochemistry
Qingbin Cui, Jing-Quan Wang, Yehuda G Assaraf, Liang Ren, Pranav Gupta, Liuya Wei, Charles R Ashby, Dong-Hua Yang, Zhe-Sheng Chen
The successful treatment of cancer has significantly improved as a result of targeted therapy and immunotherapy. However, during chemotherapy, cancer cells evolve and can acquire "multidrug resistance" (MDR), which significantly limits the efficacy of cancer treatment and impacts patient survival and quality of life. Among the approaches to reverse MDR, modulating reactive oxidative species (ROS) may represent a strategy to kill MDR cancer cells that are mechanistically diverse. ROS in cancer cells play a central role in regulating and inducing apoptosis, thereby modulating cancer cells proliferation, survival and drug resistance...
November 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Zeng Qi, Zhuo Li, Wei Li, Yunhe Liu, Cuizhu Wang, Hongqiang Lin, Jinping Liu, Pingya Li
In this study, the protective effects of pseudoginsengenin DQ (PDQ) on cisplatin (CDDP)-induced nephrotoxicity were assessed, with a primary investigation into the mechanisms involved. Our results showed that pretreatment with PDQ remarkably restored levels of blood urea nitrogen (BUN) and creatinine (CRE), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor- α (TNF- α ), and interleukin-1 β (IL-1 β ). Meanwhile, PDQ decreased the CDDP-induced overexpression of heme oxygenase 1 (HO-1), cytochrome P450 E1 (CYP2E1), TNF- α , nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in renal tissues...
November 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Teresa Arnandis, Pedro Monteiro, Sophie D Adams, Victoria Louise Bridgeman, Vinothini Rajeeve, Emanuela Gadaleta, Jacek Marzec, Claude Chelala, Ilaria Malanchi, Pedro R Cutillas, Susana A Godinho
Centrosomal abnormalities, in particular centrosome amplification, are recurrent features of human tumors. Enforced centrosome amplification in vivo plays a role in tumor initiation and progression. However, centrosome amplification occurs only in a subset of cancer cells, and thus, partly due to this heterogeneity, the contribution of centrosome amplification to tumors is unknown. Here, we show that supernumerary centrosomes induce a paracrine-signaling axis via the secretion of proteins, including interleukin-8 (IL-8), which leads to non-cell-autonomous invasion in 3D mammary organoids and zebrafish models...
November 19, 2018: Developmental Cell
Yan Jun Ma, Can Song Lu, Jian Wen Wang
Hypocrellins, fungal perylenequinones of Shiraia bambusicola are developed as important photodynamic therapy agents against cancers and viruses. Due to the limitation of the wild resources, the mycelium culture is a promising alternative for hypocrellin production. As DNA methylation has profound effects on fungal growth, development and secondary metabolism, we used both McrBC cleavage and HPLC analysis to reveal the status of DNA methylation of S. bambusicola mycelium. We found that DNA methylation is absent in mycelia, but DNA methylation inhibitor 5-azacytidine (5-AC) still induced the fluffy phenotype and decreased hypocrellin contents significantly...
2018: Frontiers in Microbiology
Nour Yahfoufi, Nawal Alsadi, Majed Jambi, Chantal Matar
This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines' synthesis, and gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways...
November 2, 2018: Nutrients
Ping Tang, Hao Dang, Jie Huang, Tao Xu, Ping Yuan, Jun Hu, Jian-Feng Sheng
The function of the NAD(P)H oxidases (NOXs) family member NOX4 is to generate reactive oxygen species (ROS), however, the molecular function of NOX4 has not been fully studied and waiting to be clarified. To elucidate the function of endogenous Nox4 in human thyroid carcinomas, papillomatosis thyroid cancer cells were used to study the cell growth by knocking down the expression of NOX4 and knocking out its functional partner p22phox/CYBA. As a result, the increasement of mitochondrial ROS(mROS) was abolished due to both knockdown of NOX4 and p22phox knockout in hypoxia, which destabilized HIF1α decreasing glycolysis and retarded cell growth...
October 26, 2018: Scientific Reports
Keywan Mortezaee, Nasser Hashemi Goradel, Peyman Amini, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Masoud Najafi, Bagher Farhood
BACKGROUND: Radiotherapy is a treatment modality for cancer. For better therapeutic efficiency, it could be used in combination with surgery, chemotherapy or immunotherapy. In addition to its beneficial therapeutic effects, exposure to radiation leads to several toxic effects on normal tissues. Also, it may induce some changes in genomic expression of tumor cells, thereby increasing the resistance of tumor cells. These changes lead to the appearance of some acute reactions in irradiated organs, increased risk of carcinogenesis, and reduction in the therapeutic effect of radiotherapy...
October 10, 2018: Current Molecular Pharmacology
Mohini A Tupurani, Chiranjeevi Padala, Kaushik Puranam, Rajesh K Galimudi, Keerthi Kupsal, Nivas Shyamala, Srilatha Gantala, Ramanjaneyulu Kummari, Sanjeeva K Chinta, Surekha R Hanumanth
Background: Oxidative stress (OS) is a key characteristic feature in cancer initiation and progression. Among multiple cancers, NADPH oxidase (NOX) dependent free radical production is implicated in oxidative stress. P22phox, a subunit of NADPH oxidase encoded by the CYBA gene has functional polymorphisms associated with various complex diseases. The present study was aimed to examine the importance and association of the functional polymorphisms of CYBA gene (-930 A/G and 242 C/T) with the oxidative stress in breast cancer (BC) development and progression...
2018: PeerJ
Yu-Hua Chu, Syuan-Wei Kao, Disline Manli Tantoh, Pei-Chieh Ko, Shou-Jen Lan, Yung-Po Liaw
The aim of this study was to investigate the association between fine particulate matter 2.5 (PM2.5 ) and oral cancer among Taiwanese men. Four linked data sources including the Taiwan Cancer Registry, Adult Preventive Medical Services Database, National Health Insurance Research Database, and Air Quality Monitoring Database were used. Concentrations of sulfur dioxide, carbon monoxide, ozone, NOx (nitrogen monoxide and nitrogen dioxide), coarse particulate matter (PM10-2.5 ) and PM2.5 in 2009 were assessed in quartiles...
October 9, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Philip Wolfe, Kenneth Davidson, Charles Fulcher, Neal Fann, Margaret Zawacki, Kirk R Baker
By-products of mobile source combustion processes, such as those associated with gasoline- and diesel-powered engines, include direct emissions of particulate matter as well as precursors to particulate matter and ground-level ozone. Human exposure to fine particulate matter with an aerodynamic diameter smaller than 2.5 μm (PM2.5 ) is associated with increased incidence of premature mortality and morbidity outcomes. This study builds upon recent, detailed source-apportionment air quality modeling to project the health-related benefits of reducing PM2...
February 10, 2019: Science of the Total Environment
Niklas Jänsch, Christian Meyners, Marius Muth, Aleksandra Kopranovic, Olaf Witt, Ina Oehme, Franz-Josef Meyer-Almes
Enzymes from the histone deacetylase (HDAC) family are highly regulated by different mechanisms. However, only very limited knowledge exists about the regulation of HDAC8, an established target in multiple types of cancer. A previous dedicated study of HDAC class I enzymes identified no redox-sensitive cysteinyl thiol in HDAC8. This is in contrast to the observation that HDAC8 preparations show different enzyme activities depending on the addition of reducing agents. In the light of the importance of HDAC8 in tumorigenesis a possible regulation by redox signaling was investigated using biochemical and biophysical methods combined with site directed mutagenesis...
September 27, 2018: Redox Biology
Terry W Moody, Lingaku Lee, Tatiana Iordanskaia, Irene Ramos-Alvarez, Paola Moreno, Howard E Boudreau, Thomas L Leto, Robert T Jensen
Pituitary adenylate cyclase activating polypeptide (PACAP) is a growth factor for lung cancer cells. PACAP-27 or PACAP-38 binds with high affinity to non-small cell lung cancer (NSCLC) cells, causing elevated cytosolic Ca2+ , increased proliferation and increased phosphorylation of extracellular regulated kinase (ERK) and the epidermal growth factor receptor (EGFR). The role of reactive oxygen species (ROS) was investigated in these processes. Addition of PACAP-38 to NCI-H838 or A549 cells increased the tyrosine phosphorylation of the EGFR, HER2 and ERK significantly by 4-, 3-, and 2-fold, respectively...
September 28, 2018: Peptides
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