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Cancer AND NadPH

Suhrid Banskota, Sadan Dahal, Eunju Kwon, Dong Young Kim, Jung-Ae Kim
PURPOSE: Over half of the colon cancer patients suffer from cancer-related events, mainly metastasis. Loss of β-catenin activity has previously been found to facilitate cancer cell dissociation and migration. Here, we aimed to investigate whether epigenetic silencing of β-catenin induces human colon cancer cell migration and/or invasion. METHODS: HCT-116, Caco-2, HT-29 and SW620 cell migration and invasion capacities were assessed using scratch wound healing and Matrigel invasion assays, respectively...
June 19, 2018: Cellular Oncology (Dordrecht)
Se-Jin Kim, Channy Park, Joon No Lee, Raekil Park
Cisplatin is an alkylating agent that interferes with DNA replication and kills proliferating carcinogenic cells. Several studies have been conducted to attenuate the side effects of cisplatin; one such side effect in cancer patients undergoing cisplatin chemotherapy is ototoxicity. However, owing to a lack of understanding of the precise mechanism underlying cisplatin-induced side effects, management of cisplatin-induced ototoxicity remains unsolved. We investigated the protective effects of fenofibrate, a PPAR-α activator, on cisplatin-induced ototoxicity...
June 13, 2018: Toxicology and Applied Pharmacology
Tsadik Habtetsion, Zhi-Chun Ding, Wenhu Pi, Tao Li, Chunwan Lu, Tingting Chen, Caixia Xi, Helena Spartz, Kebin Liu, Zhonglin Hao, Nahid Mivechi, Yuqing Huo, Bruce R Blazar, David H Munn, Gang Zhou
The inhibitory effects of cancer on T cell metabolism have been well established, but the metabolic impact of immunotherapy on tumor cells is poorly understood. Here, we developed a CD4+ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, we show that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species (ROS) in tumor cells...
May 30, 2018: Cell Metabolism
Su Jeong Ha, Jangho Lee, Joon Park, Young Ho Kim, Nam Hyouck Lee, Young Eon Kim, Kyung-Mo Song, Pahn-Shick Chang, Chul-Ho Jeong, Sung Keun Jung
Validation of nutraceutical and pharmaceutical targets is essential for the prediction of physiological and side effects. Epidemiologic evidence and molecular studies suggest that non-melanoma skin cancer is directly associated with excessive exposure to ultraviolet (UV) radiation. The aim of the present study was to evaluate the inhibitory effects of syringic acid on UVB-induced signaling and skin carcinogenesis, and determine the molecular targets. Treatment of human epidermal keratinocytes (HaCaT) cells with syringic acid resulted in the suppression of UVB-induced cyclooxygenase-2, matrix metalloproteinase-1, and prostaglandin E2 expression as well as activator protein-1 activity...
June 7, 2018: Biochemical Pharmacology
Xing Zheng, Hongxia Li
Transketolase-like 1 (TKTL1) plays an important role in the pentose phosphate pathway (PPP) branch. The main obstacle of ovarian cancer treatment is chemotherapeutic resistance. We investigated whether inhibiting TKTL1 in OC3/TAX300 cells could re-sensitize paclitaxel-resistant cells to paclitaxel and proposed a mechanism of action. Western blotting revealed that TKTL1 expression levels in OC3/Tax300 cells were significantly higher than those in OC3 cells. Inhibition of TKTL1 significantly decreased the cellular proliferation rate and IC50 for paclitaxel...
June 7, 2018: Biochemical and Biophysical Research Communications
Mohammed Khurshed, Niels Aarnoudse, Renske Hulsbos, Vashendriya V V Hira, Hanneke W M van Laarhoven, Johanna W Wilmink, Remco J Molenaar, Cornelis J F van Noorden
Isocitrate dehydrogenase ( IDH1)-1 is mutated in various types of human cancer, and the presence of this mutation is associated with improved responses to irradiation and chemotherapy in solid tumor cells. Mutated IDH1 (IDH1MUT ) enzymes consume NADPH to produce d-2-hydroxyglutarate (d-2HG) resulting in the decreased reducing power needed for detoxification of reactive oxygen species (ROS), for example. The objective of the current study was to investigate the mechanism behind the chemosensitivity of the widely-used anticancer agent cisplatin in IDH1MUT cancer cells...
June 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Xin You, Mingzhe Ma, Guoxin Hou, Yumin Hu, Xi Shi
Introduction: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) are frequently deregulated in several human malignancies, including gastric cancer (GC). NOX-derived reactive oxygen species have been reported to contribute to gastric carcinogenesis and cancer progression. However, the expression and prognostic role of individual NOX in GC patients remain elusive. Methods and materials: We investigated genetic alteration and mRNA expression of NOX family in GC patients via the cBioPortal, Human Protein Atlas, and Oncomine databases...
2018: OncoTargets and Therapy
Nikos Koundouros, George Poulogiannis
Metabolic rewiring and the consequent production of reactive oxygen species (ROS) are necessary to promote tumorigenesis. At the nexus of these cellular processes is the aberrant regulation of oncogenic signaling cascades such as the phosphoinositide 3-kinase and AKT (PI3K/Akt) pathway, which is one of the most frequently dysregulated pathways in cancer. In this review, we examine the regulation of ROS metabolism in the context of PI3K-driven tumors with particular emphasis on four main areas of research. (1) Stimulation of ROS production through direct modulation of mitochondrial bioenergetics, activation of NADPH oxidases (NOXs), and metabolic byproducts associated with hyperactive PI3K/Akt signaling...
2018: Frontiers in Oncology
Franziska Moll, Maria Walter, Flávia Rezende, Valeska Helfinger, Estefania Vasconez, Tiago De Oliveira, Florian R Greten, Catherine Olesch, Andreas Weigert, Heinfried H Radeke, Katrin Schröder
Aim: Reactive oxygen species (ROS) produced by enzymes of the NADPH oxidase family serve as second messengers for cellular signaling. Processes such as differentiation and proliferation are regulated by NADPH oxidases. In the intestine, due to the exceedingly fast and constant renewal of the epithelium both processes have to be highly controlled and balanced. Nox1 is the major NADPH oxidase expressed in the gut, and its function is regulated by cytosolic subunits such as NoxO1. We hypothesize that the NoxO1-controlled activity of Nox1 contributes to a proper epithelial homeostasis and renewal in the gut...
2018: Frontiers in Immunology
Zheng Lu, Lingling Chang, Qian Du, Yong Huang, Xiujuan Zhang, Xingchen Wu, Jie Zhang, Ruizhen Li, Zelin Zhang, Wenlong Zhang, Xiaomin Zhao, Dewen Tong
Arctigenin (ARG), one of the most active ingredients abstracted from seeds of Arctium lappa L. , has been proved to exert promising biological activities such as immunomodulatory, anti-viral, and anti-cancer etc. However, the mechanism behind its immunomodulatory function still remains elusive to be further investigated. In this study, we found that ARG had no significant effects on the cell proliferation in both porcine alveolar macrophage cell line (3D4/21) and primary porcine derived alveolar macrophage...
2018: Frontiers in Pharmacology
Laxmidhar Das, Manjula Vinayak
BACKGROUND: Warburg effect is characterized by upregulation of HIF-1 and c-Myc regulated LDH-A, even aerobically owing to hypoxic environment and alterations in oncogenes or tumor suppressor genes in cancer. Reduced antioxidant defence system in transformed cells favors higher ROS production, which plays a significant role in carcinogenesis and acts as an important regulator of NF-κB. In addition, various proinflammatory cytokines play active roles in maintenance and progression of cancer...
June 3, 2018: Anti-cancer Agents in Medicinal Chemistry
Ilaria Silvestri, Haining Lyu, Francesca Fata, Giovanna Boumis, Adriana E Miele, Matteo Ardini, Rodolfo Ippoliti, Andrea Bellelli, Ajit Jadhav, Wendy A Lea, Anton Simeonov, Qing Chen, Elias S J Arner, Gregory Rj Thatcher, Pavel A Petukhov, David L Williams, Francesco Angelucci
Members of the FAD/NAD-linked reductase family are recognized as crucial targets in drug development for cancers, inflammatory disorders, and infectious diseases. However, individual FAD/NAD reductases are difficult to inhibit in a selective manner with off target inhibition reducing usefulness of identified compounds. Thioredoxin glutathione reductase (TGR), a high molecular weight thioredoxin reductase-like enzyme, has emerged as a promising drug target for the treatment of schistosomiasis, a parasitosis afflicting more than 200 million people...
May 25, 2018: ACS Chemical Biology
Ilknur Ozgencli, Harun Budak, Mehmet Ciftci, Mustafa Anar
BACKGROUND: Thioredoxin reductase (E.C; TrxR) is a widely distributed flavoprotein that catalyzes the NADPH-dependent reduction of thioredoxin (Trx) in many cellular events such as DNA synthesis, DNA repair, angiogenesis, antioxidative defense, and regulating apoptosis. Although TrxR is indispensible in protecting cells against oxidative stress, the overexpression of TrxR is seen in many aggressive tumors. Therefore, targeted inhibition of TrxR has been accepted as a new approach for chemotherapy...
May 24, 2018: Anti-cancer Agents in Medicinal Chemistry
Fangrui Wu, Gang Cheng, Yuan Yao, Mari Kogiso, Hong Jiang, Xiao-Nan Li, Yongcheng Song
BACKGROUND: R132H mutation of isocitrate dehydrogenase 1 (IDH1) are found in ~75% of low-grade gliomas and secondary glioblastomas as well as in several other types of cancer. More chemotypes of inhibitors of IDH1(R132H) are therefore needed. OBJECTIVE: To develop a new class of IDH1(R132H) inhibitors as potent antitumor agents. METHOD: A biochemical assay was developed to find inhibitors of IDH1(R132H) mutant enzyme. Chemical synthesis and structure activity relationship studies were used to find compounds with improved potency...
May 23, 2018: Medicinal Chemistry
Sang Yeon Cho, Ju Seok Kim, Hyuk Soo Eun, Sun Hyung Kang, Eaum Seok Lee, Seok Hyun Kim, Jae Kyu Sung, Byung Seok Lee, Hyun Yong Jeong, Hee Seok Moon
BACKGROUND: The NADPH oxidase (NOX) family is overexpressed in many cancers and is associated with cancer cell proliferation and metastasis; however, little is known about the role of the NOX family in colorectal cancer (CRC). AIMS: To identify the expression of the NOX family in CRC and to investigate the relationship between the expression of NOXs with the prognosis of the patients. METHODS: In the TCGA data portal, mRNA expression data were obtained from 41 normal samples and 458 CRC samples to analyze mRNA expression and gene alteration...
May 21, 2018: Digestive Diseases and Sciences
Bin Li, Zhong Wang, Jia-Ming Xie, Gang Wang, Li-Qiang Qian, Xue-Mei Guan, Xue-Ping Shen, Zheng-Hong Qin, Gen-Hai Shen, Xiao-Qiang Li, Quan-Gen Gao
Our previous study showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) regulated ROS, autophagy, and apoptosis in response to hypoxia and chemotherapeutic drugs. Aescin, a triterpene saponin, exerts anticancer effects and increases ROS levels. The ROS is a key upstream signaling to activate autophagy. Whether there is a crosstalk between TIGAR and aescin in regulating ROS, autophagy, and apoptosis is unknown. In this study, we found that aescin inhibited cell viability and colony formation, and induced DNA damage, cell cycle arrest, and apoptosis in cancer cell lines HCT-116 and HCT-8 cells...
May 16, 2018: Acta Pharmacologica Sinica
G A Nagana Gowda
Coenzymes of cellular redox reactions and cellular energy, as well as antioxidants mediate biochemical reactions fundamental to the functioning of all living cells. Conventional analysis methods lack the opportunity to evaluate these important redox and energy coenzymes and antioxidants in a single step. Major coenzymes include redox coenzymes: NAD⁺ (oxidized nicotinamide adenine dinucleotide), NADH (reduced nicotinamide adenine dinucleotide), NADP⁺ (oxidized nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate); energy coenzymes: ATP (adenosine triphosphate), ADP (adenosine diphosphate) and AMP (adenosine monophosphate); and antioxidants: GSSG (oxidized glutathione) and GSH (reduced glutathione)...
May 14, 2018: Metabolites
Daniela Mennerich, Sakari Kellokumpu, Thomas Kietzmann
SIGNIFICANCE: Eukaryotic cells execute various functions in subcellular compartments or organelles for which cellular redox homeostasis is of importance. Apart from mitochondria, hypoxia and stress mediated formation of reactive oxygen species (ROS) were shown to modulate endoplasmic reticulum (ER) and Golgi apparatus (GA) functions. Recent Advances: Research during the last decade has improved our understanding of disulfide bond formation, protein glycosylation and secretion as well as pH and redox homeostasis in the endoplasmic reticulum (ER) and Golgi apparatus (GA)...
May 2, 2018: Antioxidants & Redox Signaling
Sho Tabata, Masatatsu Yamamoto, Hisatsugu Goto, Akiyoshi Hirayama, Maki Ohishi, Takuya Kuramoto, Atsushi Mitsuhashi, Ryuji Ikeda, Misako Haraguchi, Kohichi Kawahara, Yoshinari Shinsato, Kentaro Minami, Atsuro Saijo, Yuko Toyoda, Masaki Hanibuchi, Yasuhiko Nishioka, Saburo Sone, Hiroyasu Esumi, Masaru Tomita, Tomoyoshi Soga, Tatsuhiko Furukawa, Shin-Ichi Akiyama
Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP is identical to platelet-derived endothelial cell growth factor and contributes to tumour angiogenesis. TP induces the generation of reactive oxygen species (ROS) and enhances the expression of oxidative stress-responsive genes, such as interleukin (IL)-8. However, the mechanism underlying ROS induction by TP remains unclear. In the present study, we demonstrated that TP promotes NADPH oxidase-derived ROS signalling in cancer cells...
April 30, 2018: Scientific Reports
Ming Zhuo, Murat F Gorgun, Ella W Englander
Peripheral Nervous System (PNS) neurotoxicity caused by cancer drugs hinders attainment of chemotherapy goals. Due to leakiness of the blood nerve barrier, circulating chemotherapeutic drugs reach PNS neurons and adversely affect their function. Chemotherapeutic drugs are designed to target dividing cancer cells and mechanisms underlying their toxicity in postmitotic neurons remain to be fully clarified. The objective of this work was to elucidate progression of events triggered by antimitotic drugs in postmitotic neurons...
June 2018: Free Radical Biology & Medicine
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