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https://www.readbyqxmd.com/read/28518138/betulin-exhibits-anti-inflammatory-activity-in-lps-stimulated-macrophages-and-endotoxin-shocked-mice-through-an-ampk-akt-nrf2-dependent-mechanism
#1
Xinxin Ci, Junfeng Zhou, Hongming Lv, Qinlei Yu, Liping Peng, Shucheng Hua
Continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer. Nuclear factor erythroid 2-related factor (Nrf2), a critical transcriptional activator for antioxidative responses, has envolved to be an attractive drug target for the treatment or prevention of human diseases. In the present study, we investigated the effects and mechanisms of betulin on Nrf2 activation and its involvement in the lipopolysaccharide (LPS)-triggered inflammatory system...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28510506/signaling-at-the-crossroads-matrix-derived-proteoglycan-and-reactive-oxygen-species-signaling
#2
Madalina-Viviana Nastase, Andrea Janicova, Malgorzata Wygrecka, Liliana Schaefer
SIGNIFICANCE: Proteoglycans (PGs), besides their structural contribution, have emerged as dynamic components that mediate a multitude of cellular events. The various roles of PGs are attributed to their structure, spatial localization, and ability to act as ligands and receptors. Reactive oxygen species (ROS) are small mediators, which are generated in physiological and pathological conditions. Besides their reactivity and ability to induce oxidative stress, a growing body of data suggests that ROS signaling is more relevant than direct radical damage in development of human pathologies...
May 16, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28498822/interleukin-4-and-interleukin-13-increase-nadph-oxidase-1-related-proliferation-of-human-colon-cancer-cells
#3
Han Liu, Smitha Antony, Krishnendu Roy, Agnes Juhasz, Yongzhong Wu, Jiamo Lu, Jennifer L Meitzler, Guojian Jiang, Eric Polley, James H Doroshow
Human colon cancers express higher levels of NADPH oxidase 1 [NOX1] than adjacent normal epithelium. It has been suggested that reactive oxygen species [ROS] derived from NOX1 contribute to DNA damage and neoplastic transformation in the colon, particularly during chronic inflammatory stress. However, the mechanism(s) underlying increased NOX1 expression in malignant tumors or chronic inflammatory states involving the intestine are poorly characterized. We examined the effects of two pro-inflammatory cytokines, IL-4 and IL-13, on the regulation of NOX1...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28482870/effect-of-the-cancer-specific-shorter-form-of-human-6-phosphofructo-1-kinase-on-the-metabolism-of-the-yeast-saccharomyces-cerevisiae
#4
Darjan Andrejc, Alenka Možir, Matic Legiša
BACKGROUND: At first glance, there appears to be a high degree of similarity between the metabolism of yeast (the Crabtree effect) and human cancer cells (the Warburg effect). At the root of both effects is accelerated metabolic flow through glycolysis which leads to overflows of ethanol and lactic acid, respectively. It has been proposed that enhanced glycolytic flow in cancer cells is triggered by the altered kinetic characteristics of the key glycolytic regulatory enzyme 6-phosphofructo-1-kinase (Pfk)...
May 8, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28481367/inhibition-of-malic-enzyme-1-disrupts-cellular-metabolism-and-leads-to-vulnerability-in-cancer-cells-in-glucose-restricted-conditions
#5
S Murai, A Ando, S Ebara, M Hirayama, Y Satomi, T Hara
Malic enzyme 1 (ME1) regulates one of the main pathways that provide nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for cancer cell growth through maintenance of redox balance and biosynthesis processes in the cytoplasm. In this study, we found that ME1 inhibition disrupted metabolism in cancer cells and inhibited cancer cell growth by inducing senescence or apoptosis. In glucose-restricted culture conditions, cancer cells increased ME1 expression, and tracer experiments with labelled glutamine revealed that the flux of ME1-derived pyruvate to citrate was enhanced...
May 8, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28476935/a-schistosoma-japonicum-infection-promotes-the-expansion-of-myeloid-derived-suppressor-cells-by-activating-the-jak-stat3-pathway
#6
Quan Yang, Huaina Qiu, Hongyan Xie, Yanwei Qi, Hefei Cha, Jiale Qu, Mei Wang, Yuanfa Feng, Xin Ye, Jianbing Mu, Jun Huang
Myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immune cells from the myeloid lineage, play an important part in suppression of host immune responses during many pathologic conditions, including cancer and infectious diseases. Thus, understanding the functional diversity of these cells as well as the underlying mechanisms is crucial for the development of disease control strategies. The role of MDSCs during Schistosoma japonicum infection, however, is not clear, and there is a lack of systematic study so far...
May 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28475173/microrna-30a-attenuates-mutant-kras-driven-colorectal-tumorigenesis-via-direct-suppression-of-me1
#7
Hongxing Shen, Chuan Xing, Kaisa Cui, Yunxiao Li, Jinxiang Zhang, Runlei Du, Xiaodong Zhang, Youjun Li
Frequent KRAS mutations contribute to multiple cancers including ~40% of human colorectal cancers (CRCs). Systematic screening of 1255 microRNAs (miRNAs) identified miR-30a as a synthetic lethal in KRAS-mutant CRC cells. miR-30a was downregulated in CRCs and repressed by P65. miR-30a directly targeted malic enzyme 1 (ME1) and KRAS, and inhibited anchorage-independent growth and in vivo tumorigenesis by KRAS-mutant CRC cells. ME1 was significantly upregulated in KRAS-mutant CRCs. Eliminating ME1 by short hairpin RNA (shRNA) resulted in obviously decreased NADPH production, levels of triglyceride and fatty acid, and an inhibition of tumorigenicity of KRAS-mutant CRCs...
May 5, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28473742/nadph-oxidase-activation-contributes-to-heavy-ion-irradiation-induced-cell-death
#8
Yupei Wang, Qing Liu, Weiping Zhao, Xin Zhou, Guoying Miao, Chao Sun, Hong Zhang
Increased oxidative stress plays an important role in heavy ion radiation-induced cell death. The mechanism involved in the generation of elevated reactive oxygen species (ROS) is not fully illustrated. Here we show that NADPH oxidase activation is closely related to heavy ion radiation-induced cell death via excessive ROS generation. Cell death and cellular ROS can be greatly reduced in irradiated cancer cells with the preincubation of diphenyleneiodium, an inhibitor of NADPH oxidase. Most of the NADPH oxidase (NOX) family proteins (NOX1, NOX2, NOX3, NOX4, and NOX5) showed increased expression after heavy ion irradiation...
January 2017: Dose-response: a Publication of International Hormesis Society
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
#9
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...
May 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
#10
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...
May 16, 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
#11
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...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423654/mcl-1-regulates-reactive-oxygen-species-via-nox4-during-chemotherapy-induced-senescence
#12
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...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422720/overexpression-of-nox4-predicts-poor-prognosis-and-promotes-tumor-progression-in-human-colorectal-cancer
#13
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...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394261/folate-cycle-enzyme-mthfd1l-confers-metabolic-advantages-in-hepatocellular-carcinoma
#14
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...
May 1, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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