Enhancement of DNA synthesis and cell proliferation by 1-methylnicotinamide in rat liver cells in culture: Implication for its in vivo role

Hoshino, Jiro; Kühne, Uta; Kröger, Hans

doi:10.1016/0006-291x(82)90950-0

Cited by 20 publications

(9 citation statements)

References 19 publications

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“…The formation of MeNAM in this catabolic route has often been thought to be the only function of NNMT, with MeNAM serving as an inert, more easily excreted product compared with NAM. However, this would be to ignore data evidencing the cell growth-promoting properties of MeNAM, [131][132][133] which link to earlier data suggesting a relation between NAM methylation and cancer. [136][137][138] Nevertheless, even if the biologically inert nature of MeNAM were the case, supranormal expression of NNMT would have the capability to not only influence NAM, NAD + /H, and NADPH levels but also those of SAM, and ultimately homocysteine.…”

Section: Expression and Actions Of Nnmt And Menam In Cancermentioning

confidence: 99%

NicotinamideN-Methyltransferase in Health and Cancer

Ramsden

Waring

Barlow

et al. 2017

Int J�Tryptophan�Res

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Over the past decade, the roles of nicotinamide N-methyltransferase and its product 1-methyl nicotinamide have emerged from playing merely minor roles in phase 2 xenobiotic metabolism as actors in some of the most important scenes of human life. In this review, the structures of the gene, messenger RNA, and protein are discussed, together with the role of the enzyme in many of the common cancers that afflict people today.

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Section: Expression and Actions Of Nnmt And Menam In Cancermentioning

confidence: 99%

NicotinamideN-Methyltransferase in Health and Cancer

Ramsden

Waring

Barlow

et al. 2017

Int J�Tryptophan�Res

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“…In addition, 1-methylnicotinamide and N -acetylneuraminate were exclusively detected in the LCSCs among putative metabolites (Supplementary Table S3). Interestingly, 1-methylnicotinamide, a product of nicotinamide catabolized by nicotinamide N -methyltransferase (NNMT), stimulates cell growth of both rat hepatocellular carcinoma cells22 and human murine erythroleukemia cells23. N -acetylneuraminate, the most common sialic acid derivative in mammals, is an anticancer target because sialylation in cancer cells is associated with inhibition of apoptosis, progression, metastasis and resistance to therapy24.…”

Section: Resultsmentioning

confidence: 99%

Systems approach to characterize the metabolism of liver cancer stem cells expressing CD133

Hur

Ryu

Kim

et al. 2017

Sci Rep

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Liver cancer stem cells (LCSCs) have attracted attention because they cause therapeutic resistance in hepatocellular carcinoma (HCC). Understanding the metabolism of LCSCs can be a key to developing therapeutic strategy, but metabolic characteristics have not yet been studied. Here, we systematically analyzed and compared the global metabolic phenotype between LCSCs and non-LCSCs using transcriptome and metabolome data. We also reconstructed genome-scale metabolic models (GEMs) for LCSC and non-LCSC to comparatively examine differences in their metabolism at genome-scale. We demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. We also confirmed that MYC, a central point of regulation in cancer metabolism, was significantly up-regulated in LCSCs compared with non-LCSCs. Moreover, LCSCs tend to have less active fatty acid oxidation. In this study, the metabolic characteristics of LCSCs were identified using integrative systems analysis, and these characteristics could be potential cures for the resistance of liver cancer cells to anticancer treatments.

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“…57 Enhanced DNA synthesis and proliferation has also been shown to occur in rat liver cells in response to MNA. 58…”

Section: Discussionmentioning

confidence: 99%

“…57 Enhanced DNA synthesis and proliferation has also been shown to occur in rat liver cells in response to MNA. 58 MNA, by serving as a substrate for the enzyme AOX1/GAD-3, has recently been described as a compound able of generating a H 2 O 2 -mediated ROS signal that, at least in Drosophila, promotes lifespan and metabolic health. 11 The authors speculate that sirtuins play a key role in lifespan regulation by providing increased amounts of the MNA precursor NAM.…”

Section: Discussionmentioning

confidence: 99%

NAD metabolites interfere with proliferation and functional properties of THP-1 cells

et al. 2019

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Over the past few years the NAD-related compounds nicotinamide (NAM), nicotinamide riboside (NR) and 1-methylnicotinamide (MNA) have been established as important molecules in signalling pathways that contribute to metabolic functions of many cells, including those of the immune system. Among immune cells, monocytes/macrophages, which are the major players of inflammatory processes, are especially susceptible to the anti-inflammatory action of NAM. Here we asked whether NAM and the two other compounds have the potential to regulate differentiation and LPS-induced biological answers of the monocytic cell line THP-1. We show that treatment of THP-1 cells with NAM, NR and MNA resulted in growth retardation accompanied by enrichment of cells in the G0/G1-phase independent of p21 and p53. NAM and NR caused an increase in intracellular NAD concentrations and SIRT1 and PARP1 mRNA expression was found to be enhanced. The compounds failed to up-regulate the expression of the cell surface differentiation markers CD38, CD11b and CD14. They modulated the reactive oxygen species production and primed the cells to respond less effectively to the LPS induced TNF-α production. Our data show that the NAD metabolites interfere with early events associated with differentiation of THP-1 cells along the monocytic path and that they affect LPS-induced biological responses of the cell line.

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Enhancement of DNA synthesis and cell proliferation by 1-methylnicotinamide in rat liver cells in culture: Implication for its in vivo role

Cited by 20 publications

References 19 publications

NicotinamideN-Methyltransferase in Health and Cancer

NicotinamideN-Methyltransferase in Health and Cancer

Systems approach to characterize the metabolism of liver cancer stem cells expressing CD133

NAD metabolites interfere with proliferation and functional properties of THP-1 cells

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