scholarly journals Impact of One-Carbon Metabolism-Driving Epitranscriptome as a Therapeutic Target for Gastrointestinal Cancer

2021 ◽  
Vol 22 (14) ◽  
pp. 7278
Author(s):  
Yu Takeda ◽  
Ryota Chijimatsu ◽  
Andrea Vecchione ◽  
Takahiro Arai ◽  
Toru Kitagawa ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Cell Interaction ◽  
Therapeutic Drug ◽  
Oxygen Species ◽  
Biological Functions ◽  
Nucleotide Synthesis ◽  
Methylation Of Dna ◽  
One Carbon Metabolism ◽  
Therapeutic Compounds ◽  
Folate Cycle

One-carbon (1C) metabolism plays a key role in biological functions linked to the folate cycle. These include nucleotide synthesis; the methylation of DNA, RNA, and proteins in the methionine cycle; and transsulfuration to maintain the redox condition of cancer stem cells in the tumor microenvironment. Recent studies have indicated that small therapeutic compounds affect the mitochondrial folate cycle, epitranscriptome (RNA methylation), and reactive oxygen species reactions in cancer cells. The epitranscriptome controls cellular biochemical reactions, but is also a platform for cell-to-cell interaction and cell transformation. We present an update of recent advances in the study of 1C metabolism related to cancer and demonstrate the areas where further research is needed. We also discuss approaches to therapeutic drug discovery using animal models and propose further steps toward developing precision cancer medicine.

scholarly journals One-Carbon Metabolism Associated Vulnerabilities in Glioblastoma: A Review

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3067
Author(s):  
Kimia Ghannad-Zadeh ◽  
Sunit Das
Keyword(s):  
Cell Biology ◽  
Cell Transformation ◽  
Therapeutic Potential ◽  
Cell Metabolism ◽  
Treatment Strategies ◽  
Metabolic Reprogramming ◽  
Phenotypic Marker ◽  
Nucleotide Synthesis ◽  
One Carbon Metabolism ◽  
C Metabolism

Altered cell metabolism is a hallmark of cancer cell biology, and the adaptive metabolic strategies of cancer cells have been of recent interest to many groups. Metabolic reprogramming has been identified as a critical step in glial cell transformation, and the use of antimetabolites against glioblastoma has been investigated. One-carbon (1-C) metabolism and its associated biosynthetic pathways, particularly purine nucleotide synthesis, are critical for rapid proliferation and are altered in many cancers. Purine metabolism has also been identified as essential for glioma tumourigenesis. Additionally, alterations of 1-C-mediated purine synthesis have been identified as commonly present in brain tumour initiating cells (BTICs) and could serve as a phenotypic marker of cells responsible for tumour recurrence. Further research is required to elucidate mechanisms through which metabolic vulnerabilities may arise in BTICs and potential ways to therapeutically target these metabolic processes. This review aims to summarize the role of 1-C metabolism-associated vulnerabilities in glioblastoma tumourigenesis and progression and investigate the therapeutic potential of targeting this pathway in conjunction with other treatment strategies.

One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development

2019 ◽  
Vol 7 (1) ◽  
pp. 263-287 ◽  
Author(s):  
Constance E. Clare ◽  
Amey H. Brassington ◽  
Wing Yee Kwong ◽  
Kevin D. Sinclair
Keyword(s):  
Dna Sequences ◽  
Methylation Of Dna ◽  
Epigenetic Effects ◽  
Epigenetic Programming ◽  
Target Dna ◽  
Ethnic Variability ◽  
Associated Proteins ◽  
Epigenetic Gene Regulation ◽  
One Carbon Metabolism

One-carbon (1C) metabolism comprises a series of interlinking metabolic pathways that include the methionine and folate cycles that are central to cellular function, providing 1C units (methyl groups) for the synthesis of DNA, polyamines, amino acids, creatine, and phospholipids. S-adenosylmethionine is a potent aminopropyl and methyl donor within these cycles and serves as the principal substrate for methylation of DNA, associated proteins, and RNA. We propose that 1C metabolism functions as a key biochemical conduit between parental environment and epigenetic regulation of early development and that interindividual and ethnic variability in epigenetic-gene regulation arises because of genetic variants within 1C genes, associated epigenetic regulators, and differentially methylated target DNA sequences. We present evidence to support these propositions, drawing upon studies undertaken in humans and animals. We conclude that future studies should assess the epigenetic effects of cumulative (multigenerational) dietary imbalances contemporaneously in both parents, as this better represents the human experience.

scholarly journals Dual functional selenium-substituted hydroxyapatite

2012 ◽  
Vol 2 (3) ◽  
pp. 378-386 ◽  
Author(s):  
Yanhua Wang ◽  
Jun Ma ◽  
Lei Zhou ◽  
Jin Chen ◽  
Yonghui Liu ◽  
...  
Keyword(s):  
Precipitation Method ◽  
Oxygen Species ◽  
Apoptosis Induction ◽  
Selenium Content ◽  
Biological Functions ◽  
Osteosarcoma Cells ◽  
Dual Functional ◽  
Flow Cytometric ◽  
Co Precipitation ◽  
Dual Functions

Hydroxyapatite (HA) doped with trace elements has attracted much attention recently owing to its excellent biological functions. Herein, we use a facile co-precipitation method to incorporate selenium into HA by adding sodium selenite during synthesis. The obtained selenium-substituted HA products are needle-like nanoparticles which have  size and crystallinity that are similar to those of the pure HA nanoparticles (HANs) when the selenium content is low. HANs are found to have the ability to induce the apoptosis of osteosarcoma cells, and the anti-tumour effects are enhanced after incorporation of selenium. Meanwhile, the nanoparticles can also support the growth of bone marrow stem cells. Furthermore, the flow cytometric results indicate that the apoptosis induction of osteosarcoma cells is caused by the increased reactive oxygen species and decreased mitochondrial membrane potential. These results show that the selenium-substituted HANs are potentially promising bone graft materials in osteosarcoma treatment due to their dual functions of supporting normal cell growth and inducing tumour cell apoptosis.

scholarly journals Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring

2020 ◽  
Vol 31 (1) ◽  
pp. 635-649
Author(s):  
Angelo Harlan De Crescenzo ◽  
Alexios A Panoutsopoulos ◽  
Lyvin Tat ◽  
Zachary Schaaf ◽  
Shailaja Racherla ◽  
...  
Keyword(s):  
Folic Acid ◽  
Cellular Proliferation ◽  
De Novo ◽  
Regulation Of Gene Expression ◽  
Folate Deficiency ◽  
Nucleotide Synthesis ◽  
Biochemical Alterations ◽  
Supplement Use ◽  
Behavioral Abnormalities ◽  
Folate Cycle

Abstract Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations. Here, we show that either maternal folate deficiency or FA excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. Our findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.

scholarly journals Oxidative Stress-Driven Autophagy acROSs Onset and Therapeutic Outcome in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Fabio Ciccarone ◽  
Serena Castelli ◽  
Maria Rosa Ciriolo
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Viral Infections ◽  
Apoptotic Cell ◽  
Oxygen Species ◽  
Suppressor Mechanism ◽  
Ros Burst ◽  
Therapeutic Compounds ◽  
Chemotherapeutic Interventions

Reactive oxygen species- (ROS-) mediated autophagy physiologically contributes to management of cell homeostasis in response to mild oxidative stress. Cancer cells typically engage autophagy downstream of ROS signaling derived from hypoxia and starvation, which are harsh environmental conditions that need to be faced for cancer development and progression. Hepatocellular carcinoma (HCC) is a solid tumor for which several environmental risk factors, particularly viral infections and alcohol abuse, have been shown to promote carcinogenesis via augmentation of oxidative stress. In addition, ROS burst in HCC cells frequently takes place after administration of therapeutic compounds that promote apoptotic cell death or even autophagic cell death. The interplay between ROS and autophagy (i) in the disposal of dysfunctional mitochondria via mitophagy, as a tumor suppressor mechanism, or (ii) in the cell survival adaptive response elicited by chemotherapeutic interventions, as a tumor-promoting event, will be depicted in this review in relation to HCC development and progression.

Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

2011 ◽  
Vol 414 (3) ◽  
pp. 533-538 ◽  
Author(s):  
Richard L. Carpenter ◽  
Yue Jiang ◽  
Yi Jing ◽  
Jun He ◽  
Yon Rojanasakul ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Transformation ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals A candidate gene study of one-carbon metabolism pathway genes and colorectal cancer risk

2012 ◽  
Vol 109 (6) ◽  
pp. 984-989 ◽  
Author(s):  
Marcella Martinelli ◽  
Luca Scapoli ◽  
Gabriella Mattei ◽  
Giampaolo Ugolini ◽  
Isacco Montroni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Carbon Metabolism ◽  
Protein Function ◽  
Restriction Analysis ◽  
Likelihood Ratio Statistic ◽  
Folate Intake ◽  
Nucleotide Synthesis ◽  
Preliminary Results ◽  
Increased Risk ◽  
One Carbon Metabolism

The risk of colorectal cancer (CRC) may be influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by impaired dietary folate intake as well as by polymorphic variants in one-carbon metabolism genes. A case–control study using seventy-one CRC patients and eighty unrelated healthy controls was carried out to assess the genetic association of fifteen SNP and one insertion in nine genes belonging to the folate pathway. Polymorphism selection was based on literature data, and included those which have a known or suspected functional impact on cancer and missense polymorphisms that are most likely to alter protein function. Genotyping was performed by real-time PCR and PCR followed by restriction analysis. The likelihood ratio statistic indicated that most of the polymorphisms were not associated with the risk of CRC. However, an increased risk of CRC was observed for two variant alleles of SNP mapping on the transcobalamin 2 gene (TCN2): C776G (rs1801198) and c.1026-394T>G (rs7286680). Considering the crucial biological function played by one-carbon metabolism genes, further investigations with larger cohorts of CRC patients are needed in order to confirm our preliminary results. These preliminary results indicate that TCN2 polymorphisms can be a susceptibility factor for CRC.

Resveratrol in vitro amelioratestert-butyl hydroperoxide-induced alterations in erythrocyte membranes from young and older humans

2014 ◽  
Vol 39 (10) ◽  
pp. 1093-1097 ◽  
Author(s):  
Kanti Bhooshan Pandey ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Biological Effect ◽  
Healthy Subjects ◽  
Structural Integrity ◽  
Cell Interaction ◽  
Erythrocyte Membranes ◽  
Cell Physiology ◽  
Oxygen Species

Implication of reactive oxygen species/oxidative stress has been readily reported in etiology of aging and related manifestations. Plasma membrane as a regulator of numerous aspects of cell physiology including cell–cell interaction, solute transport, and signal transduction, provides structural integrity to the cells. The aim of the present study was to determine the effect of resveratrol administration in vitro, to evaluate the biological effect of this phytoalexin in oxidatively injured erythrocytes during aging. This study, carried out on 91 normal healthy subjects, provides experimental evidence that erythrocytes have increased oxidative damage with age. In vitro administration of resveratrol significantly attenuated deleterious effects of oxidative injury in erythrocytes from humans of all ages.

scholarly journals Tuning the Toxicity of Reactive Oxygen Species into Advanced Tumor Therapy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
An Xie ◽  
He Li ◽  
Yumei Hao ◽  
Yujia Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Tumor Therapy ◽  
Reactive Oxygen ◽  
Progress Report ◽  
Advanced Treatment ◽  
Oxygen Species ◽  
Biological Functions ◽  
Tumor Treatment ◽  
Advanced Tumor

AbstractThe biological functions and toxic effects of reactive oxygen species (ROS) are generally entangled. A large amount of ROS may cause oxidative damage to cell biomolecules, leading to cell death. Tumor treatment can be carried out by using the toxicity of ROS, and various nanosystems related to ROS have been designed. In fact, the level of active oxygen in the biological microenvironment can be regulated in advanced therapeutics via designed nanoscale engineering, which can open up a new direction of treatment with specific simplicity. In this progress report, the authors first introduced how ROS causes cell death. Then, recent studies on converting the inherent toxicity from ROS into advanced treatment tools are highlighted.

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