scholarly journals Vitamin C Transporters and Their Implications in Carcinogenesis

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3869
Author(s):  
Kinga Linowiecka ◽  
Marek Foksinski ◽  
Anna A. Brożyna
Keyword(s):  
Vitamin C ◽  
Cancer Biology ◽  
Redox Homeostasis ◽  
Regulation Of Gene Expression ◽  
Dna Demethylation ◽  
Altered Expression ◽  
Tet Proteins ◽  
Active Dna Demethylation ◽  
Hypoxic State

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe2+ dependent dioxygenases (2-OGDD), which are involved in active DNA demethylation (TET proteins), the demethylation of histones, and hypoxia processes. Therefore, vitamin C may be engaged in the regulation of gene expression or in a hypoxic state. Hence, vitamin C has acquired great interest for its plausible effects on cancer treatment. Since its conceptualization, the role of vitamin C in cancer therapy has been a controversial and disputed issue. Vitamin C is transferred to the cells with sodium dependent transporters (SVCTs) and glucose transporters (GLUT). However, it is unknown whether the impaired function of these transporters may lead to carcinogenesis and tumor progression. Notably, previous studies have identified SVCTs’ polymorphisms or their altered expression in some types of cancer. This review discusses the potential effects of vitamin C and the impaired SVCT function in cancers. The variations in vitamin C transporter genes may regulate the active transport of vitamin C, and therefore have an impact on cancer risk, but further studies are needed to thoroughly elucidate their involvement in cancer biology.

scholarly journals Ascorbic acid improves parthenogenetic embryo development through TET proteins in mice

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Wei Gao ◽  
Xianfeng Yu ◽  
Jindong Hao ◽  
Ling Wang ◽  
Minghui Qi ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Embryonic Development ◽  
Real Time Pcr ◽  
Quantitative Real Time Pcr ◽  
Qrt Pcr ◽  
Tet Proteins ◽  
Parthenogenetic Embryo ◽  
Blastocyst Rate

Abstract The TET (Ten-Eleven Translocation) proteins catalyze the oxidation of 5mC (5-methylcytosine) to 5hmC (5-hydroxymethylcytosine) and play crucial roles in embryonic development. Ascorbic acid (Vc, Vitamin C) stimulates the expression of TET proteins, whereas DMOG (dimethyloxallyl glycine) inhibits TET expression. To investigate the role of TET1, TET2, and TET3 in PA (parthenogenetic) embryonic development, Vc and DMOG treatments were administered during early embryonic development. The results showed that Vc treatment increased the blastocyst rate (20.73 ± 0.46 compared with 26.57 ± 0.53%). By contrast, DMOG reduced the blastocyst rate (20.73 ± 0.46 compared with 11.18 ± 0.13%) in PA embryos. qRT-PCR (quantitative real-time PCR) and IF (immunofluorescence) staining results revealed that TET1, TET2, and TET3 expressions were significantly lower in PA embryos compared with normal fertilized (Con) embryos. Our results revealed that Vc stimulated the expression of TET proteins in PA embryos. However, treatment with DMOG significantly inhibited the expression of TET proteins. In addition, 5hmC was increased following treatment with Vc and suppressed by DMOG in PA embryos. Taken together, these results indicate that the expression of TET proteins plays crucial roles mediated by 5hmC in PA embryonic development.

scholarly journals Glutathione S - transferases class Pi and Mi and their significance in oncology

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Zofia Marchewka ◽  
Agnieszka Piwowar ◽  
Sylwia Ruzik ◽  
Anna Długosz
Keyword(s):  
Redox Homeostasis ◽  
Current Data ◽  
Altered Expression ◽  
Potential Marker ◽  
Inflammatory Processes ◽  
Glutathione S Transferases ◽  
Endogenous Substrates ◽  
Cancer Tissues ◽  
Serum And Urine

In this article the current data, which shows that glutathione S-transferases (GST) class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi) in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

scholarly journals The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1894
Author(s):  
Marcelo Villagran ◽  
Jorge Ferreira ◽  
Miquel Martorell ◽  
Lorena Mardones
Keyword(s):  
Clinical Trials ◽  
Vitamin C ◽  
Cancer Prevention ◽  
Randomized Study ◽  
Regulation Of Gene Expression ◽  
Water Soluble ◽  
In Vitro Assays ◽  
High Concentration

Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines, and in the regulation of gene expression. In cancer, vitamin C is associated with prevention, progression, and treatment, due to its general properties or its role as a pro-oxidant at high concentration. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and transport of vitamin C into cancer cells. The reviewed studies show that vitamin C intake from natural sources can prevent the development of pulmonary and breast cancer, and that vitamin C synergizes with gemcitabine and erlotinib in pancreatic cancer. In vitro assays reveal that vitamin C synergizes with DNA-methyl transferase inhibitors. However, vitamin C was not associated with cancer prevention in a Mendelian randomized study. In conclusion, the role of vitamin C in the prevention and treatment of cancer is still an ongoing area of research. It is necessary that new phase II and III clinical trials be performed to collect stronger evidence of the therapeutic role of vitamin C in cancer.

scholarly journals L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice

2021 ◽  
Author(s):  
Wan-Qiu Peng ◽  
Gang Xiao ◽  
Bai-Yu Li ◽  
Ying-Ying Guo ◽  
Liang Guo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Intraperitoneal Administration ◽  
Dna Demethylation ◽  
Active Dna Demethylation ◽  
Diet Induced Obesity ◽  
Elevated Expression ◽  
Obesity In Mice

L-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with L-Theanine(100mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1 and other thermogenic genes. Meanwhile, administration of the mice with L-Theanine increased energy expenditure. In vitro studies indicated that L-Theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of L-Theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. L-Theanine treatment enhanced AMPKα phosphorylation both in adipocytes and in iWAT. Knockdown of AMPKα ablolished L-Theanine-induced upregulation of Prdm16 and adipocytes browning. L-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for L-Theanine-induced increase of α-KG and DNA demethylation on Prdm16 promoter. Moreover, intraperitoneal administration with L-Theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol and free fatty acid in the high fat diet-fed mice. Our results suggest a potential role of L-Theanine in combating diet-induced obesity in mice, which may involve L-Theanine-induced browning of white adipose tissue.

scholarly journals Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA

Science ◽  
2011 ◽  
Vol 333 (6047) ◽  
pp. 1303-1307 ◽  
Author(s):  
Yu-Fei He ◽  
Bin-Zhong Li ◽  
Zheng Li ◽  
Peng Liu ◽  
Yang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cultured Cells ◽  
Dna Demethylation ◽  
Detectable Level ◽  
Dna Modification ◽  
Thymine Dna Glycosylase ◽  
Tet Proteins ◽  
Active Dna Demethylation ◽  
Base Excision

The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.

scholarly journals DNA Demethylation Pathways: Recent Insights

2013 ◽  
Vol 5 ◽  
pp. GEG.S12143 ◽  
Author(s):  
Cong-jun Li
Keyword(s):  
Dna Methylation ◽  
Mammalian Cells ◽  
De Novo ◽  
Dna Demethylation ◽  
Epigenetic Mark ◽  
Sequencing Technologies ◽  
Active Dna Demethylation ◽  
Mammalian Genomes ◽  
Genome Context

DNA methylation is a major epigenetic regulatory mechanism for gene expression and cell differentiation. Until recently, it was still unclear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether or not active demethylating activity is involved. Even the role of molecules and the mechanisms underlying the processes of active demethylation itself is blurred. Emerging sequencing technologies have led to recent insights into the dynamic distribution of DNA methylation during development and the role of this epigenetic mark within a distinct genome context, such as the promoters, exons, or imprinted control regions. This review summarizes recent insights on the dynamic nature of DNA methylation and demethylation, as well as the mechanisms regulating active DNA demethylation in mammalian cells, which have been fundamental research interests in the field of epigenomics.

scholarly journals Ewing Sarcoma Protein: A Key Player in Human Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Paola Paronetto
Keyword(s):  
Ewing Sarcoma ◽  
Cancer Biology ◽  
Genome Stability ◽  
Rna Binding ◽  
Human Cancer ◽  
Neuromuscular Disorders ◽  
Regulation Of Gene Expression ◽  
Protein A ◽  
Structural Features

The Ewing sarcoma protein (EWS) is a well-known player in cancer biology for the specific translocations occurring in sarcomas. The EWS-FLI1 gene fusion is the prototypical translocation that encodes the aberrant, chimeric transcription factor, which is a landmark of Ewing tumors. In all described Ewing sarcoma oncogenes, the EWS RNA binding domains are completely missing; thus RNA binding properties are not retained in the hybrid proteins. However, it is currently unknown whether the absence of EWS function in RNA metabolism plays a role in oncogenic transformation or if EWS plays a role by itself in cancer development besides its contribution to the translocation. In this regard, recent reports have highlighted an essential role for EWS in the regulation of DNA damage response (DDR), a process that counteracts genome stability and is often deregulated in cancer cells. The first part of this review will describe the structural features of EWS and its multiple roles in the regulation of gene expression, which are exerted by coordinating different steps in the synthesis and processing of pre-mRNAs. The second part will examine the role of EWS in the regulation of DDR- and cancer-related genes, with potential implications in cancer therapies. Finally, recent advances on the involvement of EWS in neuromuscular disorders will be discussed. Collectively, the information reviewed herein highlights the broad role of EWS in bridging different cellular processes and underlines the contribution of EWS to genome stability and proper cell-cycle progression in higher eukaryotic cells.

scholarly journals Tet1 and Tet2 Protect DNA Methylation Canyons against Hypermethylation

2015 ◽  
Vol 36 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Laura Wiehle ◽  
Günter Raddatz ◽  
Tanja Musch ◽  
Meelad M. Dawlaty ◽  
Rudolf Jaenisch ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Regulation Of Gene Expression ◽  
Mechanistic Explanation ◽  
Dna Demethylation ◽  
Double Knockout ◽  
Developmental Defects ◽  
Active Dna Demethylation ◽  
Underlying Mechanisms

DNA methylation is a dynamic epigenetic modification with an important role in cell fate specification and reprogramming. The Ten eleven translocation (Tet) family of enzymes converts 5-methylcytosine to 5-hydroxymethylcytosine, which promotes passive DNA demethylation and functions as an intermediate in an active DNA demethylation process. Tet1/Tet2 double-knockout mice are characterized by developmental defects and epigenetic instability, suggesting a requirement for Tet-mediated DNA demethylation for the proper regulation of gene expression during differentiation. Here, we used whole-genome bisulfite and transcriptome sequencing to characterize the underlying mechanisms. Our results uncover the hypermethylation of DNA methylation canyons as the genomic key feature of Tet1/Tet2 double-knockout mouse embryonic fibroblasts. Canyon hypermethylation coincided with disturbed regulation of associated genes, suggesting a mechanistic explanation for the observed Tet-dependent differentiation defects. Based on these results, we propose an important regulatory role of Tet-dependent DNA demethylation for the maintenance of DNA methylation canyons, which prevents invasive DNA methylation and allows functional regulation of canyon-associated genes.

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