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https://www.readbyqxmd.com/read/28447737/17%C3%AE-estradiol-protects-against-doxorubicin-induced-cardiotoxicity-in-male-sprague-dawley-rats-by-regulating-nadph-oxidase-and-apoptosis-genes
#1
Xiao-Juan Zhang, Xiao-Qing Cao, Chun-Sheng Zhang, Zhuo Zhao
Doxorubicin (DOX) is one of the most effective chemotherapeutic agents for the treatment of a number of malignancies. However, its use is limited by serious cardiotoxic effects, for which there are currently no reliable pharmacologic therapies. Estrogen has exhibited protective effects against cardiac stressors in male and female animal models; however, its effects on DOX‑induced cardiotoxicity remain unknown. High mortality and morbidity rates have been observed in patients with cancer worldwide, and DOX is often administered to a greater number of men than women...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28427229/nadph-accumulation-is-responsible-for-apoptosis-in-breast-cancer-cells-induced-by-fatty-acid-synthase-inhibition
#2
Yanfen Cui, Pan Xing, Yuanyuan Wang, Miao Liu, Li Qiu, Guoguang Ying, Binghui Li
Fatty acid synthase (FAS), as a key enzyme involved in de novo lipogenesis, is highly expressed in many cancers. FAS inhibition induces cell death in vivo and in vitro, rendering FAS as an attractive target for cancer therapy, but the defined mechanism is still not well understood. Herein, we confirmed that FAS was highly expressed in breast cancers and FAS inhibition by its inhibitors or knockdown induced apoptosis in breast cancer cells. Our results showed that a significantly high level of reactive oxygen species was induced but not responsible for apoptosis in breast cancer cells by FAS inhibition...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423703/artocarpin-an-isoprenyl-flavonoid-induces-p53-dependent-or-independent-apoptosis-via-ros-mediated-mapks-and-akt-activation-in-non-small-cell-lung-cancer-cells
#3
Ming-Horng Tsai, Ju-Fang Liu, Yao-Chang Chiang, Stephen Chu-Sung Hu, Lee-Fen Hsu, Yu-Ching Lin, Zih-Chan Lin, Hui-Chun Lee, Mei-Chuan Chen, Chieh-Liang Huang, Chiang-Wen Lee
Artocarpin has been shown to exhibit cytotoxic effects on different cancer cells, including non-small cell lung carcinoma (NSCLC, A549). However, the underlying mechanisms remain unclear. Here, we explore both p53-dependent and independent apoptosis pathways in artocarpin-treated NSCLC cells. Our results showed that artocarpin rapidly induced activation of cellular protein kinases including Erk1/2, p38 and AktS473. Inhibition of these protein kinases prevented artocarpin-induced cell death. Moreover, artocarpin-induced phosphorylation of these protein kinases and apoptosis were mediated by induction of reactive oxygen species (ROS), as pretreatment with NAC (a ROS scavenger) and Apocynin (a Nox-2 inhibitor) blocked these events...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423654/mcl-1-regulates-reactive-oxygen-species-via-nox4-during-chemotherapy-induced-senescence
#4
Abeba Demelash, Lukas W Pfannenstiel, Li Liu, Brian R Gastman
Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers and is believed to enhance tumorigenic potential and chemotherapy resistance through the inhibition of apoptosis and senescence. We previously reported that Mcl-1's regulation of chemotherapy-induced senescence (CIS) is dependent on its ability to prevent reactive oxygen species (ROS) generation. In this report, we demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically mitochondrial ROS, and that these events are upstream of activation of the DNA damage response, another necessary step toward senescence...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422720/overexpression-of-nox4-predicts-poor-prognosis-and-promotes-tumor-progression-in-human-colorectal-cancer
#5
Xiao-Lu Lin, Li Yang, Seng-Wang Fu, Wen-Feng Lin, Yun-Jie Gao, Hao-Yan Chen, Zhi-Zheng Ge
NADPH oxidase 4 (NOX4), a major source of reactive oxygen species (ROS) production, has been increasingly reported to be involved in tumorigenesis and/or tumor progression, but limited data are available regarding the role of NOX4 in colorectal carcinoma (CRC). We retrieved six independent investigations from Oncomine database and found that NOX4 is highly expressed in CRC tissues compared with corresponding normal controls. Similar results were also found in clinical specimens at both mRNA and protein levels...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394261/folate-cycle-enzyme-mthfd1l-confers-metabolic-advantages-in-hepatocellular-carcinoma
#6
Derek Lee, Iris Ming-Jing Xu, David Kung-Chun Chiu, Robin Kit-Ho Lai, Aki Pui-Wah Tse, Lynna Lan Li, Cheuk-Ting Law, Felice Ho-Ching Tsang, Larry Lai Wei, Cerise Yuen-Ki Chan, Chun-Ming Wong, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Cancer cells preferentially utilize glucose and glutamine, which provide macromolecules and antioxidants that sustain rapid cell division. Metabolic reprogramming in cancer drives an increased glycolytic rate that supports maximal production of these nutrients. The folate cycle, through transfer of a carbon unit between tetrahydrofolate and its derivatives in the cytoplasmic and mitochondrial compartments, produces other metabolites that are essential for cell growth, including nucleotides, methionine, and the antioxidant NADPH...
April 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28384067/mir-101-enhances-cisplatin-induced-dna-damage-through-decreasing-nicotinamide-adenine-dinucleotide-phosphate-levels-by-directly-repressing-tp53-induced-glycolysis-and-apoptosis-regulator-expression-in-prostate-cancer-cells
#7
Shiqiao Huang, Zhiguo Yang, Yong Ma, Yiyong Yang, Shangren Wang
Tp53-induced glycolysis and apoptosis regulator (TIGAR) enhances the pentose phosphate pathway, thereby contributing directly to DNA repair due to generation of nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate, two key precursors of DNA synthesis and repair. Targetscan database showed that miR-101 was predicted to potentially target TIGAR. Therefore, we speculated that miR-101 could enhance cisplatin-induced DNA damage by directly repressing TIGAR expression in prostate cancer cells...
April 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28375879/glycine-metabolism-in-skeletal-muscle-implications-for-metabolic-homeostasis
#8
René Koopman, Marissa K Caldow, Daniel J Ham, Gordon S Lynch
PURPOSE OF REVIEW: The review summarizes the recent literature on the role of glycine in skeletal muscle during times of stress. RECENT FINDINGS: Supplemental glycine protects muscle mass and function under pathological conditions. In addition, mitochondrial dysfunction in skeletal muscle leads to increased cellular serine and glycine production and activation of NADPH-generating pathways and glutathione metabolism. These studies highlight how glycine availability modulates cellular homeostasis and redox status...
April 3, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28364658/novel-2-benzylthio-5-1-3-4-oxadiazol-2-yl-benzenesulfonamides-with-anticancer-activity-synthesis-qsar-study-and-metabolic-stability
#9
Jarosław Sławiński, Krzysztof Szafrański, Aneta Pogorzelska, Beata Żołnowska, Anna Kawiak, Katarzyna Macur, Mariusz Belka, Tomasz Bączek
A series of novel 2-benzylthio-4-chloro-5-(5-substituted 1,3,4-oxadiazol-2-yl)benzenesulfonamides (4-27) have been synthesized as potential anticancer agents. MTT assay was carried out to determine the cytotoxic activity against three human cancer cell lines: colon cancer HCT-116, breast cancer MCF-7 and cervical cancer HeLa as well as to determine the influence on human keratinocyte cell line HaCaT. Relatively high (IC50: 7-17 μM) cytostatic activity and selectivity against HeLa cell line was found for compounds 6, 7, 9-11 and 16...
March 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28353636/zinc-and-oxidative-stress-current-mechanisms
#10
REVIEW
Dilina do Nascimento Marreiro, Kyria Jayanne Clímaco Cruz, Jennifer Beatriz Silva Morais, Jéssica Batista Beserra, Juliana Soares Severo, Ana Raquel Soares de Oliveira
Oxidative stress is a metabolic dysfunction that favors the oxidation of biomolecules, contributing to the oxidative damage of cells and tissues. This consequently contributes to the development of several chronic diseases. In particular, zinc is one of the most relevant minerals to human health, because of its antioxidant properties. This review aims to provide updated information about the mechanisms involved in the protective role of zinc against oxidative stress. Zinc acts as a co-factor for important enzymes involved in the proper functioning of the antioxidant defense system...
March 29, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28352233/aldo-keto-reductase-akr1c1-akr1c4-functions-regulation-and-intervention-for-anti-cancer-therapy
#11
REVIEW
Chen-Ming Zeng, Lin-Lin Chang, Mei-Dan Ying, Ji Cao, Qiao-Jun He, Hong Zhu, Bo Yang
Aldo-keto reductases comprise of AKR1C1-AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. Recent studies have provided evidences of strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Mechanistically, most studies focus on the catalytic-dependent function of AKR1C isoforms, like their impeccable roles in prostate cancer, breast cancer, and drug resistance due to the broad substrates specificity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28342583/affinity-chromatographic-methodologies-based-on-immobilized-voltage-dependent-anion-channel-isoform-1-and-application-in-protein-ligand-interaction-analysis-and-bioactive-compounds-screening-from-traditional-medicine
#12
Qian Li, Pan Qiao, Xiu Chen, Jing Wang, Liujiao Bian, Xiaohui Zheng
Voltage dependent anion channel isoform 1 (VDAC-1) serves as an attractive target of anti-cancer drugs by mediating the entry and exit of metabolites between cytoplasm and mitochondria. This work reports on the preparation of a VDAC-1-based bioaffinity chromatographic stationary phase by linking the protein on lecithin modified microspheres. An assay of chromatographic methods including frontal analysis, zonal elution, injection dependent analysis and nonlinear chromatography were utilized to investigate the bindings of ATP, NADH and NADPH to VDAC-1...
April 28, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28330872/nadph-oxidase-1-supports-proliferation-of-colon-cancer-cells-by-modulating-reactive-oxygen-species-dependent-signal-transduction
#13
Agnes Juhasz, Susan Markel, Shikha Gaur, Han Liu, Jiamo Lu, Guojian Jiang, Xiwei Wu, Smitha Antony, Yongzhong Wu, Giovanni Melillo, Jennifer L Meitzler, Diana C Haines, Donna Butcher, Krishnendu Roy, James H Doroshow
Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates superoxide, is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G1/S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28314989/inhibition-of-got1-sensitizes-colorectal-cancer-cells-to-5-fluorouracil
#14
Chengyu Hong, Jian Zheng, Xiaoling Li
PURPOSE: Almost all colorectal cancer (CRC) cell lines are known to overexpress aspartate aminotransferase (GOT1), which potentially regulates the intracellular levels of reactive oxygen species (ROS) via the production of NADPH, and supports tumor growth. In our study, the role of GOT1 in the anticancer efficacy of 5-fluorouracil (5-FU) was examined. METHODS: HCT116, SW480, and HT-29 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against GOT1...
March 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28314603/overexpression-of-msk1-is-associated-with-tumor-aggressiveness-and-poor-prognosis-in-colorectal-cancer
#15
Xinhui Fu, Xinjuan Fan, Jun Hu, Hongzhi Zou, Zhiting Chen, Qi Liu, Beibei Ni, Xiaoli Tan, Qiao Su, Jingxuan Wang, Lei Wang, Jianping Wang
BACKGROUND/AIMS: Mitogen- and stress-activated protein kinase 1 (MSK1) has recently been implicated in cell proliferation and neoplastic transformation. However, the involvement of MSK1 in colorectal cancer (CRC) has not been addressed. This study aimed to evaluate the expression and potential functions of MSK1 in CRC. METHODS: The MSK1 expression was investigated by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction. The associations between clinicopathological characteristics and MSK1 expression were assessed...
February 20, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28297659/oncogene-selective-sensitivity-to-synchronous-cell-death-following-modulation-of-the-amino-acid-nutrient-cystine
#16
Ioannis Poursaitidis, Xiaomeng Wang, Thomas Crighton, Christiaan Labuschagne, David Mason, Shira L Cramer, Kendra Triplett, Rajat Roy, Olivier E Pardo, Michael J Seckl, Scott W Rowlinson, Everett Stone, Richard F Lamb
Cancer cells reprogram their metabolism, altering both uptake and utilization of extracellular nutrients. We individually depleted amino acid nutrients from isogenic cells expressing commonly activated oncogenes to identify correspondences between nutrient supply and viability. In HME (human mammary epithelial) cells, deprivation of cystine led to increased cell death in cells expressing an activated epidermal growth factor receptor (EGFR) mutant. Cell death occurred via synchronous ferroptosis, with generation of reactive oxygen species (ROS)...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28290443/inhibition-of-hepatic-lipogenesis-enhances-liver-tumorigenesis-by-increasing-antioxidant-defence-and-promoting-cell-survival
#17
Marin E Nelson, Sujoy Lahiri, Jenny D Y Chow, Frances L Byrne, Stefan R Hargett, David S Breen, Ellen M Olzomer, Lindsay E Wu, Gregory J Cooney, Nigel Turner, David E James, Jill K Slack-Davis, Carolin Lackner, Stephen H Caldwell, Kyle L Hoehn
The metabolic pathway of de novo lipogenesis is frequently upregulated in human liver tumours, and its upregulation is associated with poor prognosis. Blocking lipogenesis in cultured liver cancer cells is sufficient to decrease cell viability; however, it is not known whether blocking lipogenesis in vivo can prevent liver tumorigenesis. Herein, we inhibit hepatic lipogenesis in mice by liver-specific knockout of acetyl-CoA carboxylase (ACC) genes and treat the mice with the hepatocellular carcinogen diethylnitrosamine (DEN)...
March 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28272757/aldosterone-activates-the-oncogenic-signals-erk1-2-and-stat3-via-redox-regulated-mechanisms
#18
Nina Queisser, Nicole Schupp, Eva Schwarz, Christina Hartmann, Gerardo G Mackenzie, Patricia I Oteiza
Epidemiological studies found an increased risk for kidney cancer in hypertensive patients, of which a subgroup has high aldosterone (Ald) levels. We recently showed that Ald is genotoxic both in kidney tubular cells and in rats with mineralocorticoid-mediated hypertension. The present work investigated in vitro and in vivo, if the oxidative stress-mediated activation of the ERK1/2 pathway, and its downstream target STAT3, could be one mechanism involved in the potential oncogenic capability of excess Ald exposure...
March 8, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28272754/hyperpolarized-%C3%AE-1-13-c-gluconolactone-as-a-probe-of-the-pentose-phosphate-pathway
#19
Karlos X Moreno, Crystal E Harrison, Matthew E Merritt, Zoltan Kovacs, Craig R Malloy, A Dean Sherry
The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis), but simple methods for detecting changes in flux through this pathway are not available. MRI of hyperpolarized (13) C-enriched metabolites offers considerable potential as a rapid, non-invasive tool for detecting changes in metabolic fluxes. In this study, hyperpolarized δ-[1-(13) C]gluconolactone was used as a probe to detect flux through the oxidative portion of the pentose phosphate pathway (PPPox ) in isolated perfused mouse livers...
March 8, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28267564/development-of-17%C3%AE-hydroxysteroid-dehydrogenase-type-3-as-a-target-in-hormone-dependent-prostate-cancer-therapy
#20
REVIEW
Xiaohui Ning, Yan Yang, Hong Deng, Qihao Zhang, Yadong Huang, Zhijian Su, Yongmei Fu, Qi Xiang, Shu Zhang
17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed almost exclusively in the testes and specifically converts the weak androgenic androstenedione to active testosterone (T) in the presence of NADPH. Additionally, studies have demonstrated that 17β-HSD3 is over-expressed in hormone-dependent prostate cancer. T, which interacts with the androgen receptor (AR), eventually stimulates the growth of prostate cancer cells. Defects in T synthesis or action impair the development of the male phenotype during embryogenesis and cause the autosomal recessive disorder male pseudohermaphroditism...
March 4, 2017: Steroids
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