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https://www.readbyqxmd.com/read/28548968/aldose-reductase-interacts-with-akt1-to-augment-hepatic-akt-mtor-signaling-and-promote-hepatocarcinogenesis
#1
Jia-Xing Zhao, Ya-Wei Yuan, Cheng-Fu Cai, Dong-Yan Shen, Mao-Li Chen, Feng Ye, Yan-Jun Mi, Qi-Cong Luo, Wang-Yu Cai, Wei Zhang, Ying Long, Yong Zeng, Guo-Dong Ye, Shu-Yu Yang
Marked up-regulation of aldose reductase (AR) is reportedly associated with the development of hepatocellular carcinoma (HCC). We investigated how aberrantly overexpressed AR might promote oncogenic transformation in liver cells and tissues. We found that overexpressed AR interacted with the kinase domain of AKT1 to increase AKT/mTOR signaling. In both cultured liver cancer cells and liver tissues in DEN-induced transgenic HCC model mice, we observed that AR overexpression-induced AKT/mTOR signaling tended to enhance lactate formation and hepatic inflammation to enhance hepatocarcinogenesis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28543190/effects-of-shrna-mediated-silencing-of-pkm2-gene-on-aerobic-glycolysis-cell-migration-cell-invasion-and-apoptosis-in-colorectal-cancer-cells
#2
Xiao-Ling Yan, Xue-Bin Zhang, Ran Ao, Lin Guan
This study aims to explore the effects of shRNA-mediated silencing on Pyruvate kinase type M2 (PKM2) gene during aerobic glycolysis in colorectal cancer (CRC) cells. CRC tissues and adjacent normal tissues were obtained from 136 patients diagnosed with qRT-PCR, Western blotting and immunohistochemistry (IHC) were performed to detect mRNA and protein expressions of PKM2. CRC cells were divided into a blank, vector and PKM2-shRNA groups. Hexokinase (HK) and PKM2 activity were both determined by glucose-6-phosphate dehydrogenase (G-6-PD) coupled colorimetric assay and enzyme coupling rate method...
May 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28539279/-monocarboxylate-transporter-1-enhances-the-sensitivity-of-breast-cancer-cells-to-3-bromopyruvate-in-vitro
#3
Qi-Xiang Li, Pei Zhang, Fang Liu, Xian-Zhi Wang, Lu Li, Zhong-Kun Wang, Chen-Chen Jiang, Hai-Lun Zheng, Hao Liu
OBJECTIVE: To investigate the role of monocarboxylate transporter 1 (MCT1) in enhancing the sensitivity of breast cancer cells to 3-bromopyruvate (3-BrPA). METHODS: The inhibitory effect of 3-BrPA on the proliferation of breast cancer cells was assessed with MTT assay, and brominated propidium bromide single staining flow cytometry was used for detecting the cell apoptosis. An ELISA kit was used to detect the intracellular levels of hexokinase II, lactate dehydrogenase, lactate, and adenosine triphosphate, and Western blotting was performed to detect the expression of MCT1...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28539246/consideration-of-alternative-causes-of-lactic-acidosis-thiamine-deficiency-in-malignancy
#4
Ryan K Dean, Rogin Subedi, Dalvir Gill, Amitpal Nat
Lactic acidosis is a common metabolic acidosis characterized by increased serum lactate and is usually associated with a decreased blood pH. Lactic acidosis has many different causes but has been differentiated into type A, hypoxic causes, and type B, non-hypoxic causes. Tissue hypoxia, type A, is the most common cause, usually secondary to processes such as sepsis and multi-organ failure. Type A must be differentiated from type B in the correct clinical setting as treatments are vastly different. Type B causes may include drug side-effects, toxins, enzymatic defects, inherited or acquired, any of which may lead to overproduction or underutilization of lactate...
May 15, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28530221/micu1-drives-glycolysis-and-chemoresistance-in-ovarian-cancer
#5
Prabir K Chakraborty, Soumyajit Banerjee Mustafi, Xunhao Xiong, Shailendra Kumar Dhar Dwivedi, Vasyl Nesin, Sounik Saha, Min Zhang, Danny Dhanasekaran, Muralidharan Jayaraman, Robert Mannel, Kathleen Moore, Scott McMeekin, Da Yang, Rosemary Zuna, Kai Ding, Leonidas Tsiokas, Resham Bhattacharya, Priyabrata Mukherjee
Cancer cells actively promote aerobic glycolysis to sustain their metabolic requirements through mechanisms not always clear. Here, we demonstrate that the gatekeeper of mitochondrial Ca(2+) uptake, Mitochondrial Calcium Uptake 1 (MICU1/CBARA1) drives aerobic glycolysis in ovarian cancer. We show that MICU1 is overexpressed in a panel of ovarian cancer cell lines and that MICU1 overexpression correlates with poor overall survival (OS). Silencing MICU1 in vitro increases oxygen consumption, decreases lactate production, inhibits clonal growth, migration and invasion of ovarian cancer cells, whereas silencing in vivo inhibits tumour growth, increases cisplatin efficacy and OS...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529605/mutual-regulation-of-mir-199a-5p-and-hif-1%C3%AE-modulates-the-warburg-effect-in-hepatocellular-carcinoma
#6
Binkui Li, Liru He, Dinglan Zuo, Wei He, Yongjin Wang, Yuanping Zhang, Wenwu Liu, Yunfei Yuan
The Warburg effect is one of the major metabolic changes of cancer cells, which characterized by high level of glycolysis even in the presence of oxygen. However, the role of microRNAs (miRNAs) in regulating the glycolytic switch in cancer cells has not been well explored. In this study, we demonstrated that miR-199a-5p acts as a suppressor of the Warburg effect in hepatocellular carcinoma (HCC). MiR-199a-5p directly targets the 3'-untranslated region (UTR) of hypoxia-inducible factor-1α (HIF-1α), thereby suppressing glucose uptake, lactate production, cell growth, and expression of HIF-1α downstream glycolytic genes of HCC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529153/model-of-vascular-desmoplastic-multispecies-tumor-growth
#7
Chin F Ng, Hermann B Frieboes
We present a three-dimensional nonlinear tumor growth model composed of heterogeneous cell types in a multicomponent-multispecies system, including viable, dead, healthy host, and extra-cellular matrix (ECM) tissue species. The model includes the capability for abnormal ECM dynamics noted in tumor development, as exemplified by pancreatic ductal adenocarcinoma, including dense desmoplasia typically characterized by a significant increase of interstitial connective tissue. An elastic energy is implemented to provide elasticity to the connective tissue...
May 18, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28528091/antiproliferative-activity-of-ontario-grown-onions-against-colorectal-adenocarcinoma-cells
#8
Abdulmonem I Murayyan, Cynthya M Manohar, Gordon Hayward, Suresh Neethirajan
Cancer is the leading cause of mortality in Canada and other industrialized nations; the development of new/improved cancer therapies is desperately needed and continues to be a major focus of cancer research. Flavonoids, which are found in high levels in onions, have been shown to exert antiproliferative and potentially anti-cancer activities. To test their therapeutic potential, we assessed the antiproliferative, cytotoxic, apoptosis-inducing, and anti-migratory activities of five onion varieties grown in Ontario against human adenocarcinoma (Caco-2) cells...
June 2017: Food Research International
https://www.readbyqxmd.com/read/28526992/epithelial-mesenchymal-transition-emt-in-metastatic-breast-cancer-in-omani-women
#9
Ritu Lakhtakia, Adil Aljarrah, Muhammad Furrukh, Shyam S Ganguly
Breast cancer (BC) in Oman affects younger women and has a more aggressive course. Clinical and biological variables like age, pregnancy, tumor size, type, grade, receptor expression and proliferation predict disease aggression but there is no direct predictor of metastasis except lymphovascular invasion. Epithelial-mesenchymal transition (EMT) is characterized by epithelial cells losing epithelial and acquiring mesenchymal morpho-immunophenotypic characteristics. In tumors, EMT-like transitions may signify a metastatic phenotype and have features in common with cancer stem cells (CSC) which show resistance to chemotherapy...
May 19, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#10
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522974/low-dose-paclitaxel-inhibits-tumor-cell-growth-by-regulating-glutaminolysis-in-colorectal-carcinoma-cells
#11
Chaoxiang Lv, Hao Qu, Wanyun Zhu, Kaixiang Xu, Anyong Xu, Baoyu Jia, Yubo Qing, Honghui Li, Hong-Jiang Wei, Hong-Ye Zhao
Paclitaxel (PTX) is a natural alkaloid isolated from the bark of a tree, Taxus brevifolia, and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM) have rarely been illuminated. Here we report a new antitumor mechanism of low-dose PTX in colorectal carcinoma cells. We treated colorectal carcinoma HCT116 cells with PTX at 0.1 and 0.3 nM for 0, 1, 2, or 3 days, and found that low-dose PTX inhibits cell growth without altering cell morphology and cell cycle...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28522001/cytotoxic-effect-of-a-mannogalactoglucan-extracted-from-agaricus-bisporus-on-hepg2-cells
#12
Amanda do Rocio Andrade Pires, Andrea Caroline Ruthes, Silvia Maria Suter Correia Cadena, Marcello Iacomini
A mannogalactoglucan (RK2-Ab; Mw 1.8×10(4)gmol(-1)) composed by Man (27.3%), Gal (24.4%) and Glc (48.3%) was extracted and characterized from Agaricus bisporus, and its biological activity was evaluated on human hepatocarcinoma cells (HepG2). The partially-O-methylated alditol acetates together with the NMR data suggest the main chain to be composed of α-d-Galp (32.8%) and β-d-Glcp (37.0%) units (1→6)-linked, with β-d-Manp (14.6%), as non-reducing end units, substituting the side chains at O-2 (α-d-Galp units; 3...
August 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28516269/%C3%AE-alanine-intercede-metabolic-recovery-for-amelioration-of-human-cervical-and-renal-tumors
#13
Muthuraman Pandurangan, Gansukh Enkhtaivan, Bhupendra Mistry, Rahul V Patel, Sohyun Moon, Doo Hwan Kim
β-Alanine is a non-essential amino acid and presents as a major component of various sports supplements. It is a non-proteogenic amino acid, formed in vivo by degradation of carnosine, anserine, balenine, and dihydrouracil. The present study was aimed at investigating the anti-tumor effects of β-alanine in renal and cervical tumor cells. Sulforhodamine-B assay and flow cytometric analysis were used to measure cell viability. Lactate dehydrogenase (LDH) expression was analyzed using FITC-conjugated fluorescent antibody...
May 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28514652/thymidine-catabolism-as-a-metabolic-strategy-for-cancer-survival
#14
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, Masaki Hanibuchi, Yasuhiko Nishioka, Saburo Sone, Hiroyasu Esumi, Masaru Tomita, Tomoyoshi Soga, Tatsuhiko Furukawa, Shin-Ichi Akiyama
Thymidine phosphorylase (TP), a rate-limiting enzyme in thymidine catabolism, plays a pivotal role in tumor progression; however, the mechanisms underlying this role are not fully understood. Here, we found that TP-mediated thymidine catabolism could supply the carbon source in the glycolytic pathway and thus contribute to cell survival under conditions of nutrient deprivation. In TP-expressing cells, thymidine was converted to metabolites, including glucose 6-phosphate, lactate, 5-phospho-α-D-ribose 1-diphosphate, and serine, via the glycolytic pathway both in vitro and in vivo...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514181/folic-acid-modulates-dmba-tpa-induced-changes-in-skin-of-mice-a-study-relevant-to-carcinogenesis
#15
Ashwani Koul, Navneet Kaur, Neha Arora Chugh
The present study was aimed at investigating the modulatory effects of folic acid (FA) on early stages of chemically induced skin cancer. For this, a two-stage model of skin tumorigenesis was employed. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for two weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for six weeks on the depilated skin of mice, and FA was administered orally at a dose of 40 microgram/animal for 10 weeks daily...
May 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28512002/cell-surface-g-protein-coupled-receptors-for-tumor-associated-metabolites-a-direct-link-to-mitochondrial-dysfunction-in-cancer
#16
REVIEW
Bojana Ristic, Yangzom D Bhutia, Vadivel Ganapathy
Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of mitochondrial function is one of the most significant changes that occurs in tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and epigenetics. In particular, three mitochondrial enzymes are inactivated in cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3-hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to regulation via acetylation/deacetylation...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28511405/evaluation-of-acute-oral-toxicity-of-ethanol-leaves-extract-of-catharanthus-roseus-in-wistar-albino-rats
#17
Venkateswar Rao Vutukuri, M C Das, Muralidhar Reddy, Siva Prabodh, Padma Sunethri
INTRODUCTION: Herbal drugs have gained importance globally in the treatment of various diseases. Catharanthus roseus is traditionally used as an anti diabetic and anti cancer drug. To the best of our knowledge limited data are available on acute and sub acute toxicity of C. roseus extract despite its wide spread use in traditional medicine. The present study was under taken to evaluate the acute oral toxicity of the ethanol leaves extract of C. roseus. AIM: To investigate the acute oral toxic effects of ethanol leaves extract of C...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28505181/overexpression-of-pyruvate-dehydrogenase-kinase-1-in-retinoblastoma-a-potential-therapeutic-opportunity-for-targeting-vitreous-seeds-and-hypoxic-regions
#18
Swatishree Sradhanjali, Devjyoti Tripathy, Suryasnata Rath, Ruchi Mittal, Mamatha M Reddy
Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic reprogramming of tumors, is induced in several tumors including glioblastoma, breast cancer and melanoma. However, the role played by PDK1 is not studied in retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in RB clinical samples, and studied its inhibition as a strategy to decrease cell growth and migration. We show that PDK1 is specifically overexpressed in RB patient samples especially in vitreous seeds and hypoxic regions and cell lines compared to control retina using immunohistochemistry and real-time PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28504908/mammea-longifolia-planch-and-triana-fruit-extract-induces-cell-death-in-the-human-colon-cancer-cell-line-sw480-via-mitochondria-related-apoptosis-and-activation-of-p53
#19
Chunmei Li, Yoonhwa Jeong, Misook Kim
The methanol extract of Mammea longifolia Planch. and Triana (M. longifolia) fruit was studied for anticancer and apoptotic effects in the SW480 colon cancer cell line. The apoptotic and necrotic effects of M. longifolia were detected by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) and lactate dehydrogenase assays, respectively. One hundred μg/mL of the extract killed ∼82.4% of the cells; however, 2% of the death was related to necrosis. The morphological changes in M. longifolia-stimulated SW480 cells were observed directly by light microscopy...
May 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28502718/mitochondrial-nd5-mutation-mediated-elevated-ros-regulates-apoptotic-pathway-epigenetically-in-a-p53-dependent-manner-for-generating-pro-cancerous-phenotypes
#20
Rajnish Kumar Singh, Sunil Saini, Dileep Verma, Ponnusamy Kalaiarasan, Rameshwar N K Bamezai
We have previously observed concomitant events of mutations in mitochondrial and nuclear genes, along with elevated reactive oxygen species (ROS) and differential methylation within the promoters of nuclear genes in tumors and in vitro experiments of tumorigenesis. These observations have made it pertinent to replicate and understand the role of acquired mitochondrial condition in tuning a cell to accomplish a pro-cancerous state. Using a codon optimized vector system for exogenous over-expression and mitochondrial localization; we have characterized here the role of over-expressed wild type mtND5 and one of its non-synonymous somatic mutation, ND5:P265H...
May 11, 2017: Mitochondrion
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