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Cancer AND NOX

Aaron Wilson, Vasily A Yakovlev
Cancer development and progression have been linked to oxidative stress, a condition characterized by unbalanced increase in ROS and RNS production. The main endogenous initiators of the redox imbalance in cancer cells are defective mitochondria, elevated NOX activity, and uncoupled NOS3. Traditionally, most attention has been paid to direct oxidative damage to DNA by certain ROS. However, increase in oxidative DNA lesions does not always lead to malignancy. Hence, additional ROS-dependent, pro-carcinogenic mechanisms must be important...
October 19, 2016: Free Radical Biology & Medicine
Scott Whitehouse, Pei-Lin Chen, Anna L Greenshields, Mat Nightingale, David W Hoskin, Karen Bedard
BACKGROUND: Many plant-derived chemicals have been studied for their potential benefits in ailments including inflammation, cancer, neurodegeneration, and cardiovascular disease. The health benefits of phytochemicals are often attributed to the targeting of reactive oxygen species (ROS). However, it is not always clear whether these agents act directly as antioxidants to remove ROS, or whether they act indirectly by blocking ROS production by enzymes such as NADPH oxidase (NOX) enzymes, or by influencing the expression of cellular pro- and anti- oxidants...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Florian Rouaud, Jean-Luc Boucher, Anny Slama-Schwok, Stéphane Rocchi
Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite the spectacular achievements of targeted therapies (BRAF inhibitors) or immuno-therapies (anti-CTLA4 or anti-PD1), most patients with melanoma will need additional treatments. Here we used a photoactive NADPH analogue called NS1 to induce cell death by inhibition of NADPH oxidases NOX in melanoma cells, including melanoma cells isolated from patients. In contrast, healthy melanocytes growth was unaffected by NS1 treatment...
October 14, 2016: Oncotarget
Weiyue Zheng, Masataka Umitsu, Ishaan Jagan, Charles W Tran, Noboru Ishiyama, Michael BeGora, Kiyomi Araki, Pamela S Ohashi, Mitsuhiko Ikura, Senthil K Muthuswamy
The polarity protein Scribble (SCRIB) regulates apical-basal polarity, directional migration and tumour suppression in Drosophila and mammals. Here we report that SCRIB is an important regulator of myeloid cell functions including bacterial infection and inflammation. SCRIB interacts directly with the NADPH oxidase (NOX) complex in a PSD95/Dlg/ZO-1 (PDZ)-domain-dependent manner and is required for NOX-induced reactive oxygen species (ROS) generation in culture and in vivo. On bacterial infection, SCRIB localized to phagosomes in a leucine-rich repeat-dependent manner and promoted ROS production within phagosomes to kill bacteria...
October 3, 2016: Nature Cell Biology
Mai M Abdelmageed, Reem N El-Naga, Ebtehal El-Demerdash, Mohamed M Elmazar
Sorafenib is the only chemotherapeutic agent currently approved for unresectable hepatocellular carcinoma (HCC). However, poor response rates have been widely reported. Indole-3-carbinol (I3C) is a potential chemopreventive phytochemical. The present study aimed to explore the potential chemomodulatory effects of I3C on sorafenib in HCC cells as well as the possible underlying mechanisms. I3C exhibited a greater cytotoxicity in HepG2 cells compared to Huh-7 cells (p < 0.0001). Moreover, the co-treatment of HepG2 cells with I3C and sorafenib was more effective (p = 0...
2016: Scientific Reports
Kunihiro Ito, Akinobu Ota, Takayuki Ono, Toshiki Nakaoka, Md Wahiduzzaman, Sivasundaram Karnan, Hiroyuki Konishi, Akifumi Furuhashi, Tomio Hayashi, Yoichi Yamada, Yoshitaka Hosokawa, Yoshiaki Kazaoka
NADPH oxidases, also known as the Nox family, are major sources of reactive oxygen species generation that regulate redox-sensitive signaling pathways. Recent studies have implicated the Nox family in cancer development and progression. However, the involvement of its members in the development of oral squamous cell carcinoma (OSCC) remains to be elucidated. To clarify this issue, we first analyzed mRNA expression of Nox/Duox family members (Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2) in five OSCC cell lines...
September 5, 2016: Oncology Reports
Zhengle Zhang, Qingke Duan, Hengqiang Zhao, Tao Liu, Heshui Wu, Qiang Shen, Chunyou Wang, Tao Yin
Gemcitabine, the standard chemotherapy drug for advanced pancreatic cancer, has shown limited benefits because of profound chemoresistance. However, the mechanism involved remains unclear. Cancer stem cells exhibit great tumorigenicity and are closely correlated with drug resistance and tumor relapse. In this study, we demonstrated that certain doses of gemcitabine increased the ratios of CD24(+) and CD133(+) cells and the expression of stemness-associated genes such as Bmi1, Nanog, and Sox2. The enhancement of stemness after gemcitabine treatment was accompanied by increased cell migration, chemoresistance, and tumorigenesis...
November 1, 2016: Cancer Letters
Gagan Deep, Rahul Kumar, Dhanya K Nambiar, Anil K Jain, Anand M Ramteke, Natalie J Serkova, Chapla Agarwal, Rajesh Agarwal
Hypoxia is associated with aggressive phenotype and poor prognosis in prostate cancer (PCa) patients suggesting that PCa growth and progression could be controlled via targeting hypoxia-induced signaling and biological effects. Here, we analyzed silibinin (a natural flavonoid) efficacy to target cell growth, angiogenesis and metabolic changes in human PCa, LNCaP and 22Rv1 cells under hypoxic condition. Silibinin treatment inhibited the proliferation, clonogenicity and endothelial cells tube formation by hypoxic (1% O2 ) PCa cells...
August 17, 2016: Molecular Carcinogenesis
Ming Han, Tianhui Zhang, Lei Yang, Zitong Wang, Junzhong Ruan, Xiujun Chang
BACKGROUND: Lung cancer is a leading cause of death worldwide. Considerable studies have reported that NADPH oxidase (NOX) expression or activity may play an important role in the tumorigenesis of lung cancer. However, the results are inconsistent. Thus, a systematic review and meta-analysis were conducted in this study. METHODS: A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3)...
July 2016: Journal of Thoracic Disease
Lenora Ann Pluchino, Shambhunath Choudhary, Hwa-Chain Robert Wang
Safe and effective combination chemotherapy regimens against breast cancer are lacking. We used our cellular system, consisting of the non-cancerous human breast epithelial MCF10A cell line and its derived tumorigenic, oncogenic H-Ras-expressing, MCF10A-Ras cell line, to investigate the effectiveness of a combination chemotherapy regimen in treating breast cancer cells using two FDA-approved agents, cisplatin and FK228. Cisplatin and FK228 significantly, synergistically, and preferentially induced death and reduced drug resistance of MCF10A-Ras versus MCF10A cells...
October 10, 2016: Cancer Letters
Maria Monrad, Ahmad Sajadieh, Jeppe Schultz Christensen, Matthias Ketzel, Ole Raaschou-Nielsen, Anne Tjønneland, Kim Overvad, Steffen Loft, Mette Sørensen
BACKGROUND: Atrial fibrillation is the most common sustained arrhythmia and associated with cardiovascular morbidity and mortality. The few studies conducted on short-term effects of air pollution on episodes of atrial fibrillation indicates a positive association, though not consistently. OBJECTIVES: The aim of this study was to evaluate the long-term impact of traffic-related air pollution on incidence of atrial fibrillation in the general population. METHODS: In the Danish Diet, Cancer, and Health cohort of 57,053 people aged 50-64 years at enrolment in 1993-1997, we identified 2,700 cases of first-ever hospital admission for atrial fibrillation from enrolment to end of follow-up in 2011...
July 29, 2016: Environmental Health Perspectives
Kaikai Shen, Fangfang Lu, Jianling Xie, Minfeng Wu, Bo Cai, Yurong Liu, Hong Zhang, Hongsheng Tan, Yingyi Pan, Hongxi Xu
Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2...
July 13, 2016: Oncotarget
Sen Lian, Yong Xia, Trong Thuan Ung, Pham Ngoc Khoi, Hyun Joong Yoon, Nam Ho Kim, Kyung Keun Kim, Young Do Jung
Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1β-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1β-induced IL-8 mRNA and protein expression as well as IL-8 promoter activity...
June 15, 2016: Toxicology
Peter G Wells, Shama Bhatia, Danielle M Drake, Lutfiya Miller-Pinsler
In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms...
June 2016: Birth Defects Research. Part C, Embryo Today: Reviews
Gursev S Dhaunsi, Mayra Alsaeid, Saghir Akhtar
BACKGROUND: Phytanic acid (PA) has been implicated in development of cancer and its defective metabolism is known to cause life-threatening conditions, such as Refsum disease, in children. To explore molecular mechanisms of phytanic acid-induced cellular pathology, we investigated its effect on NADPH oxidase (NOX) and epidermal growth factor receptor (EGFR) in rat aortic smooth muscle cells (RASMC). METHODS: Smooth muscle cells were isolated from rat aortae using enzymic digestion with collagenase and elastase...
2016: Lipids in Health and Disease
Sang Yun Ha, Yong-Han Paik, Jung Wook Yang, Min Ju Lee, Hyunsik Bae, Cheol-Keun Park
BACKGROUND/AIMS: Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated reactive oxygen species contribute to various liver diseases, including hepatocellular carcinoma (HCC). Uncertainties remain regarding the prognostic relevance of NOX1 and NOX4 protein expression in HCC. METHODS: NOX1 and NOX4 protein expression was examined by using immunohistochemistry in tumor tissue from 227 HCC patients who underwent hepatectomy. RESULTS: High immunoreactivity for NOX1 was observed in 197 (86...
September 15, 2016: Gut and Liver
Gagan Deep, Gati K Panigrahi
Prostate cancer (PCA) is the leading malignancy in men and the second leading cause of cancer-related deaths. Hypoxia (low O2 condition) is considered an early event in prostate carcinogenesis associated with an aggressive phenotype. In fact, clinically, hypoxia and hypoxia-related biomarkers are associated with treatment failure and disease progression. Hypoxia-inducible factor 1 (HIF-1) is the key factor that is activated under hypoxia, and mediates adaptation of cells to hypoxic conditions through regulating the expression of genes associated with angiogenesis, epithelial-to-mesenchymal transition (EMT), metastasis, survival, proliferation, metabolism, sternness, hormone-refractory progression, and therapeutic resistance...
2015: Critical Reviews in Oncogenesis
Jeanette Therming Jørgensen, Martin Søes Johansen, Line Ravnskjær, Klaus Kaae Andersen, Elvira Vaclavik Bräuner, Steffen Loft, Matthias Ketzel, Thomas Becker, Jørgen Brandt, Ole Hertel, Zorana Jovanovic Andersen
BACKGROUND: Air pollution has been considered a potent environmental risk factor for neuropathology through neuroinflammation and oxidative stress, which might also cause brain tumour formation. However, epidemiological evidence on the association between air pollution and brain tumours in humans is sparse, with no data on exposure to particles. In this study we aim to examine associations between long-term exposure to ambient air pollution and risk for development of brain tumours. METHODS: We used the Danish Nurse Cohort with 28,731 female nurses (age≥44years) recruited in 1993 or 1999 when self-reported information on lifestyle was collected...
July 2016: Neurotoxicology
Sanjay Premi, Douglas E Brash
Sunlight's ultraviolet wavelengths induce cyclobutane pyrimidine dimers (CPDs), which then cause mutations that lead to melanoma or to cancers of skin keratinocytes. In pigmented melanocytes, we found that CPDs arise both instantaneously and for hours after UV exposure ends. Remarkably, the CPDs arising in the dark originate by a novel pathway that resembles bioluminescence but does not end in light: First, UV activates the enzymes nitric oxide synthase (NOS) and NADPH oxidase (NOX), which generate the radicals nitric oxide (NO) and superoxide (O2(-)); these combine to form the powerful oxidant peroxynitrite (ONOO(-))...
August 2016: DNA Repair
Mahboobeh Pordeli, Maryam Nakhjiri, Maliheh Safavi, Sussan Kabudanian Ardestani, Alireza Foroumadi
BACKGROUND: Cancer results from a series of molecular changes that alter the normal function of cells. Breast cancer is the second leading cause of cancer death in women. To develop novel anticancer agents, new series of chromen derivatives were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines. METHOD: The growth inhibitory activities of synthesized hexahydrobenzo chromen-4-one were screened against six human cancer cell lines using an in vitro cell culture system (MTT assay)...
June 1, 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
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