Nucleotide biosynthesis arrest by silencing SHMT1 function via vitamin B6-coupled vector and effects on tumor growth inhibition

Pandey, Shambhavi; Garg, Pankaj; Lee, Somin; Choung, Han‐Wool; Choung, Yun‐Hoon; Choung, Pill‐Hoon; Chung, Jong Hoon

doi:10.1016/j.biomaterials.2014.07.045

Cited by 28 publications

(20 citation statements)

References 35 publications

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“…Arginine succinate synthetase is a ligase that is involved in amino acid metabolism, signaling pathways, and cell growth processes in cardiovascular diseases (Valeev et al, 2016). Several reactions in vitamin B 6 metabolic pathway were catalyzed by Pyridoxamine 5'-phosphate oxidase and pyridoxine kinase which contribute to neurotransmitter and amino acid metabolism (Pandey et al, 2014;Huang et al, 2016;Ramos et al, 2017;Kim et al, 2018). In this study, the above enzyme scores in the 3DG-2DG comparison were higher than in the 2DG-TCPS comparison which also indicate the 3DG can enhance the proliferation of NSCs.…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation

Fang

Zhang

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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Graphene consists of two-dimensional sp2-bonded carbon sheets, a single or a few layers thick, which has attracted considerable interest in recent years due to its good conductivity and biocompatibility. Three-dimensional graphene foam (3DG) has been demonstrated to be a robust scaffold for culturing neural stem cells (NSCs) in vitro that not only supports NSCs growth, but also maintains cells in a more active proliferative state than 2D graphene films and ordinary glass. In addition, 3DG can enhance NSCs differentiation into astrocytes and especially neurons. However, the underlying mechanisms behind 3DG's effects are still poorly understood. Metabolism is the fundamental characteristic of life and provides substances for building and powering the cell. Metabolic activity is tightly tied with the proliferation, differentiation, and self-renewal of stem cells. This study focused on the metabolic reconfiguration of stem cells induced by culturing on 3DG. This study established the correlation between metabolic reconfiguration metabolomics with NSCs cell proliferation rate on different scaffold. Several metabolic processes have been uncovered in association with the proliferation change of NSCs. Especially, culturing on 3DG triggered pathways that increased amino acid incorporation and enhanced glucose metabolism. These data suggested a potential association between graphene and pathways involved in Parkinson's disease. Our work provides a very useful starting point for further studies of NSC fate determination on 3DG.

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Section: Discussionmentioning

confidence: 99%

Three-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation

Fang

Zhang

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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“…Recently, C1 metabolic enzymes were shown to be novel therapeutic targets for cancer. Pandey et al (13) showed that inhibition of SHMT1 with targeted siRNAs reduced tumor size in a mouse xenograft model. Pickman et al (14) demonstrated inhibition of acute myeloid leukemia cells by MTHFD2 knockdown-induced suppression of TCA in vivo.…”

Section: Therapeutic Targets In C1 Metabolismmentioning

confidence: 99%

The one-carbon metabolism pathway highlights therapeutic targets for gastrointestinal cancer (Review)

Konno

Asai

Kikuchi

et al. 2017

International Journal of Oncology

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After the initial use of anti-folates for treatment of malignancies, folate metabolism has emerged as a rational diagnostic and therapeutic target in gastrointestinal cancer. The one-carbon metabolic pathway, which comprises three critical reactions (i.e., folate and methionine cycles), underlies this effect in conjunction with the trans-sulfuration pathway. Understanding of the one-carbon metabolism pathway has served to unravel the link between the causes and effects of cancer phenotypes leading to several seminal discoveries such as that of diadenosine tri-phosphate hydrolase, microRNAs, 5-FU and, more recently, trifluridine. In the folate cycle, glycine and serine fuel the mitochondrial enzymes SHMT2, MTHFD2 and ALDH1L2, which play critical roles in the cancer survival and proliferation presumably through purine production. In the methionine cycle, S-adenocyl methionine serves hydrocarbons and polyamines that are critical for the epigenetic controls. The trans-sulfuration pathway is a critical component in the synthesis of glutathione, which is involved in the production of reactive oxygen species in cancer stem cells. Therefore, characterization of one-carbon metabolism is indispensable to the development of precision medicine in the context of cancer diagnostics and therapeutics. In the present study, we review the historical issues associated with one-carbon metabolism and highlight the recent advances in cancer research.

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“…Choline can be irreversibly oxidized to betaine, providing one-carbon units in the conversion of homocysteine (Hcy) to methionine and the generation of the universal methyl donor S-adenosylmethionine (SAM) 9 . Previous studies have shown that one-carbon metabolism involves alterations in the biosynthesis of nucleotides and DNA methylation, which are thought to be implicated in carcinogenesis 10, 11 . Thus, it was hypothesized that the dietary intake of one-carbon related nutrients, such as choline, betaine and methionine, may play an important role in the development and progression of cancer.…”

Section: Introductionmentioning

confidence: 99%

Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study

Zhou

Chen

Zhou

et al. 2017

Sci Rep

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The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency questionnaire were used to collect general information and dietary intake information. Conditional logistic regression showed a significantly inverse association between total choline and betaine intakes and PLC risk. The multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for PLC for the top (vs. bottom) tertile were 0.34 (0.24–0.49; P -trend < 0.001) for total choline and 0.67 (0.48–0.93; P -trend = 0.011) for betaine. No significant association was observed between the intake of methionine and PLC risk (P > 0.05). For individual choline compounds, higher consumptions of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin were associated with a lower PLC risk (all P-trend < 0.05). The studied associations were not significantly modified by the folate intake (P-interactions: 0.488–0.890). Our findings suggest that higher choline and betaine intakes may be associated with a lower risk of PLC.

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Nucleotide biosynthesis arrest by silencing SHMT1 function via vitamin B6-coupled vector and effects on tumor growth inhibition

Cited by 28 publications

References 35 publications

Three-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation

Three-Dimensional Graphene Enhances Neural Stem Cell Proliferation Through Metabolic Regulation

The one-carbon metabolism pathway highlights therapeutic targets for gastrointestinal cancer (Review)

Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study

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