Possible mechanisms of cancer prevention by nicotinamide

Buqué, Aitziber; Bloy, Norma; Kroemer, Guido; Galluzzi, Lorenzo

doi:10.1111/bph.15096

Cited by 12 publications

(10 citation statements)

References 69 publications

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“…This observation is initially counterintuitive given the fact that alpha-tocopherol, beta-sitosterol, and nicotinamide are potential anticancer compounds [ 17 , 18 , 19 ]. For example, alpha-tocopherol exhibits superior antioxidant and anti-inflammatory properties via downregulation of transcription factor NF-kB activation [ 17 ]; beta-sitosterol and nicotinamide modulate multiple cell signaling pathways, including cell proliferation, angiogenesis, metastasis, inflammation, genomic stability, and immune-response [ 19 , 20 , 21 ]. However, compared to the AIN, the proinflammatory impact of HFD-induced obesity may outweigh the beneficial effects of these compounds (e.g., alpha-tocopherol); subsequently, AOM treatment induces a higher number of colonic ACF in the HFD group compared to the AIN group [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet

et al. 2021

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Consumption of a high-fat diet (HFD) links obesity to colon cancer in humans. Our data show that a HFD (45% energy fat versus 16% energy fat in an AIN-93 diet (AIN)) promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation in a mouse cancer model. However, the underlying metabolic basis remains to be determined. In the present study, we hypothesize that AOM treatment results in different plasma metabolomic responses in diet-induced obese mice. An untargeted metabolomic analysis was performed on the plasma samples by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found that 53 of 144 identified metabolites were different between the 4 groups of mice (AIN, AIN + AOM, HFD, HFD + AOM), and sparse partial least-squares discriminant analysis showed a separation between the HFD and HFD + AOM groups but not the AIN and AIN + AOM groups. Moreover, the concentrations of dihydrocholesterol and cholesterol were inversely associated with AOM-induced colonic ACF formation. Functional pathway analyses indicated that diets and AOM-induced colonic ACF modulated five metabolic pathways. Collectively, in addition to differential plasma metabolomic responses, AOM treatment decreases dihydrocholesterol and cholesterol levels and alters the composition of plasma metabolome to a greater extent in mice fed a HFD compared to the AIN.

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Section: Discussionmentioning

confidence: 99%

Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet

et al. 2021

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“…Cellular content of NAM mainly derives from daily diet, such as poultry, beef, and fish; however, a recent study demonstrated gut microbiota as a potential alternative source of NAM for the host ( Blacher et al., 2019 ). Lastly, NAM can also be formed from NAD + by NAD + -consuming enzymes, such as sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38 ( Buque et al., 2021 ; Rajman et al., 2018 ). NAM has been reported to boost NAD + cellular content in several cell types ( Hara et al., 2007 ; Rajman et al., 2018 ; Yu et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide breaks effector CD8 T cell responses by targeting mTOR signaling

Agliano¹,

Karginov²,

Ménoret³

et al. 2022

iScience

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“…Nicotinamide (NAM) is the amide form of niacin (vitamin B3 or vitamin PP). It is a precursor of nicotinamideadenine dinucleotide NAD + [1] and is known to play an essential role in energy metabolism and to act in several tissues including skin [2], nervous system [3,4], and muscles [5]. Its metabolic pathway is related to tryptophan metabolism [6].…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide inhibits melanoma in vitro and in vivo

Scatozza

Moschella

D’Arcangelo

et al. 2020

J Exp Clin Cancer Res

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Background Even though new therapies are available against melanoma, novel approaches are needed to overcome resistance and high-toxicity issues. In the present study the anti-melanoma activity of Nicotinamide (NAM), the amide form of Niacin, was assessed in vitro and in vivo. Methods Human (A375, SK-MEL-28) and mouse (B16-F10) melanoma cell lines were used for in vitro investigations. Viability, cell-death, cell-cycle distribution, apoptosis, Nicotinamide Adenine Dinucleotide+ (NAD+), Adenosine Triphosphate (ATP), and Reactive Oxygen Species (ROS) levels were measured after NAM treatment. NAM anti-SIRT2 activity was tested in vitro; SIRT2 expression level was investigated by in silico transcriptomic analyses. Melanoma growth in vivo was measured in thirty-five C57BL/6 mice injected subcutaneously with B16-F10 melanoma cells and treated intraperitoneally with NAM. Interferon (IFN)-γ-secreting murine cells were counted with ELISPOT assay. Cytokine/chemokine plasmatic levels were measured by xMAP technology. Niacin receptors expression in human melanoma samples was also investigated by in silico transcriptomic analyses. Results NAM reduced up to 90% melanoma cell number and induced: i) accumulation in G1-phase (40% increase), ii) reduction in S- and G2-phase (about 50% decrease), iii) a 10-fold increase of cell-death and 2.5-fold increase of apoptosis in sub-G1 phase, iv) a significant increase of NAD+, ATP, and ROS levels, v) a strong inhibition of SIRT2 activity in vitro. NAM significantly delayed tumor growth in vivo (p ≤ 0.0005) and improved survival of melanoma-bearing mice (p ≤ 0.0001). About 3-fold increase (p ≤ 0.05) of Interferon-gamma (IFN-γ) producing cells was observed in NAM treated mice. The plasmatic expression levels of 6 cytokines (namely: Interleukin 5 (IL-5), Eotaxin, Interleukin 12 (p40) (IL12(p40)), Interleukin 3 (IL-3), Interleukin 10 (IL-10) and Regulated on Activation Normal T Expressed and Secreted (RANTES) were significantly changed in the blood of NAM treated mice, suggesting a key role of the immune response. The observed inhibitory effect of NAM on SIRT2 enzymatic activity confirmed previous evidence; we show here that SIRT2 expression is significantly increased in melanoma and inversely related to melanoma-patients survival. Finally, we show for the first time that the expression levels of Niacin receptors HCAR2 and HCAR3 is almost abolished in human melanoma samples. Conclusion NAM shows a relevant anti-melanoma activity in vitro and in vivo and is a suitable candidate for further clinical investigations.

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Possible mechanisms of cancer prevention by nicotinamide

Cited by 12 publications

References 69 publications

Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet

Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High-Fat Diet Compared to an AIN-93 Diet

Nicotinamide breaks effector CD8 T cell responses by targeting mTOR signaling

Nicotinamide inhibits melanoma in vitro and in vivo

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