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The impact of NAD metabolism on cancer is particularly complex, because cells need adequate NAD to protect themselves against DNA damage and cancer, and the immune system needs NAD to fight cancer cells, but some cancers rely on NAD levels to reproduce.

ARTICLE: Does NR Cause Cancer?


Here are the studies:

Aug 31, 2023

Cancer - Aging

Aging Cell

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice

Li, Wenxuan


This mouse study is the first to show NR's potential to be a therapeutic agent for delayed effects of acute radiation exposure in patients receiving radiotherapy and exposed populations.

Aug 31, 2023

Cancer - Aging - Radiation

Aging Cell

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice

Li, Wenxuan


This mouse study is the first to show NR's potential to be a therapeutic agent for delayed effects of acute radiation exposure in patients receiving radiotherapy and exposed populations.

Aug 24, 2023

Cancer - rhabdomyosarcoma

Clinical Cancer Research

Inhibition of NAD+-dependent metabolic processes induces cellular necrosis and tumor regression in rhabdomyosarcoma models

McKay-Corkum, Grace B.


We have identified NAMPT as a dependency in rhabdomyosarcoma (RMS), a malignancy for which novel therapies are critically needed. Here we describe the effect of NAMPT inhibition on RMS proliferation and metabolism in vitro and in vivo….Most cell lines experienced profound depletion of ATP with subsequent irreversible necrotic cell death. Importantly, loss of NAD and glycolytic activity were confirmed in orthotopic in vivo models, which exhibited complete tumor regressions...RMS is highly vulnerable to NAMPT inhibition.

Aug 8, 2023


Cell Metabolism

Emerging therapies in cancer metabolism

Xio, Yi


Inhibiting the rate-limiting enzyme nicotinamide phosphoribosyl transferase (NAMPT) to block NAD+ synthesis has been extensively studied preclinically to restrain tumor growth. However, early-phase clinical trials of NAMPT inhibitors yielded modest results with significant toxicities. Alternative methods, such as identifying sensitive populations and combining NAMPT inhibitors with other therapies, are warranted. Furthermore, recent studies have revealed new concepts of NAD+ metabolism, including its involvement in signal transduction, posttranslational modifications, and epigenetic regulation. For instance, NAD+ promoted the expression of programmed cell death 1 ligand 1 (PD-L1) through epigenetic mechanisms in hepatocellular carcinoma (HCC), contributing to tumor immune evasion. Combining NAD+ replenishment with anti-PD-L1 therapy effectively repressed tumor growth in preclinical models. The controversial role of NAD+ metabolism reflects the complexity of regulating redox metabolism for cancer therapy.

Jul 21, 2023

Metabolism - Cancer - Chemotherapy


Nicotinamide Mononucleotide Versus Nicotinamide Riboside in The Protective Effects of Cisplatin-induced DNA Damage in HeLa Cells

Qiu, Shuting


NR is more effective than NMN in maintaining DNA integrity in cisplatin-treated cells.

Apr 23, 2023

Cancer - Lung - Metabolism


High-Dosage NMN Promotes Ferroptosis to Suppress Lung Adenocarcinoma Growth through the NAM-Mediated SIRT1–AMPK–ACC Pathway

Zhang, Mingjiong


Most previous studies have shown that exogenous NMN cannot be directly used by cells and needs to be decomposed into NAM and NR.... In our study, the results were in accordance with those of previous studies…

Mar 17, 2023

Cancer ⎼ Liver


Nicotinamide Adenine Dinucleotide Precursor Suppresses Hepatocellular Cancer Progression in Mice

Pang, Nengzhi


In this study, we report for the first time that nicotinamide riboside (NR) supplementation could alleviate cancer metastasis in tumor-bearing mice and enhance the maintenance of body weight at the late stage of cancer. Our results reveal that NAD precursor may be a novel treatment for the prevention of HCC progression....,NR supplementation alleviated malignancy-induced weight loss and metastasis to lung in nude mice...NR supplementation decreased metastasis to the bone and liver...NR supplementation also significantly decreased the size of allografted tumors and extended the survival time... In summary, our results supply evidence that boosting NAD levels by supplementing NR alleviates HCC progression and metastasis, which may serve as an effective treatment for the suppression of liver cancer progression.

Mar 3, 2023

Cancer - Chemotherapy

Journal of Experimental & Clinical Cancer Research

NAD pool as an antitumor target against cancer stem cells in head and neck cancer

Navas, Lola E.


The coinhibition of NAMPT and NAPRT improved the efficacy of antitumor treatment, indicating that the reduction in the NAD pool is important to prevent tumor growth.

Jan 23, 2023

Cancer - Breast


NAD+ supplementation limits triple-negative breast cancer metastasis via SIRT1-P66Shc signaling

Jiang, Yi


Here, we show that NAD+ supplement suppresses tumor metastasis in a Triple Negative Breast Cancer Model...Overall, we demonstrate that NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.

Dec 27, 2022

Cancer - Chemotherapy


Nicotinamide Mononucleotide Administration Prevents Doxorubicin-Induced Cardiotoxicity and Loss in Physical Activity in Mice

Margier, Marielle


NMN significantly increased tissue levels of NAD+ and its metabolites and improved survival and bodyweight loss in both experimental models. In addition, NMN protected against Doxo-induced cardiotoxicity and loss of physical function in acute and chronic studies, respectively. In the heart, NMN prevented Doxo-induced transcriptomic changes related to mitochondrial function, apoptosis, oxidative stress, inflammation and p53, and promyelocytic leukemia nuclear body pathways. Overall, our results suggest that NMN could prevent Doxo-induced toxicity in heart and skeletal muscle.

Dec 2, 2022

Cancer - Chemotherapy


The CD73 immune checkpoint promotes tumor cell metabolic fitness

Allard, David


We demonstrated that CD73 promote tumor growth in a cancer-cell autonomous manner by increasing metabolic fitness. This in turn favors cancer cell adaptation to nutrient-deprived microenvironments and cytotoxic stress by increasing OXPHOS, aspartate biosynthesis and DNA repair. Our study highlights new therapeutic opportunities that may be exploited in novel combination anti-cancer strategies.

Oct 28, 2022

Cancer - Chemotherapy


Intravenous Nicotinamide Riboside Administration Has a Cardioprotective Effect in Chronic Doxorubicin-Induced Cardiomyopathy

Podyacheva, Ekaterina


We demonstrated that NR intravenous administration decreases cardiac-muscle fibrous-tissue formation in chronic doxorubicin-induced cardiotoxicity development...Moreover, a pronounced protective effect of NR on the cardiovascular system was demonstrated...Simultaneously, the preventive NR administration had a more significant protective effect on the animal’s body as a whole.

Oct 1, 2022

Cancer - Skin

Journal of Drugs in Dermatology

A Narrative Review of Nicotinamide Adenine Dinucleotide (NAD)+ Intermediates Nicotinamide Riboside and Nicotinamide Mononucleotide for Keratinocyte Carcinoma Risk Reduction

Kahn, Benjamin


Oral nicotinamide (NAM) supplementation has been shown to decrease the incidence of keratinocyte carcinoma (KC) in high-risk skin cancer patients. NAM is a nicotinamide adenine dinucleotide (NAD+) intermediate and thus directly leads to increased NAD+. This increase in NAD+ is believed to be responsible for NAM’s impact on keratinocyte carcinoma risk. NAD+ has protective cellular effects and is a necessary cofactor for DNA repair, helping to prevent potentially oncogenic mutations. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are NAD+ intermediates like NAM...

Oct 1, 2022

Cancer - Breast

Biosensors and Bioelectronics

A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism

Maric, Tamara


Our results demonstrate that NR supplementation results in a significant increase in cancer prevalence and metastases of TNBC to the brain. These results outline the important role of powerful nutraceuticals like NR in cancer metabolism and the need to personalize their use in certain patient populations.

Jul 22, 2022

Brain - Cancer - NRH

Cancers (Basel)

Overcoming Temozolomide Resistance in Glioblastoma via Enhanced NAD+ Bioavailability and Inhibition of Poly-ADP-Ribose Glycohydrolase

Li, Jianfeng


Using the NAD precursor NRH to raise NAD levels in an incurable type of brain cancer (Glioblastoma multiforme or GBM) significantly increased the effectiveness of a type of chemotherapy (Temozolomide or TMZ) that is commonly used to treat GBM.

Jul 15, 2022

Metabolism - Cancer - Niacin


Structure-Based Identification and Biological Characterization of New NAPRT Inhibitors

Franco, Jorge


NAPRT displays marked tissue [specificity] and is mostly present in several catabolic healthy mammalian tissues including the heart, kidney, liver, and small intestine. In tissues that express the NAPRT protein, NA is the preferred precursor of NAD.

Jun 27, 2022

Neurons - Neuropathy - Cancer - Chemotherapy

Neuro-Oncology Advances

Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation

Acklin, Scarlett


We show that NR, an NAD+ precursor and pharmacologic activator of SIRT2, effectively prevents and alleviates CIPN in mice. We present in vitro and in vivo genetic evidence to illustrate the specific dependence on SIRT2 of NR-mediated CIPN mitigation. Importantly, we demonstrate that NAD+ mediates SIRT2-dependent neuroprotection without inhibiting cisplatin cytotoxic activity against cancer cells. NAD+ may, in fact, further sensitize certain cancer cell types to cisplatin.

May 23, 2022

NAM - Cancer - Prostate

Frontiers in Molecular Biosciences

CD38-Induced Apoptosis and Mitochondrial Damage is Restored by Nicotinamide in Prostate Cancer

Kanayama, Mayuko


...CD38 expression is consistently silenced by methylation in prostate cancer and progressively downregulated in advanced castration-resistant prostate cancer, suggesting a connection between NAD+ and prostate carcinogenesis as well as prostate cancer progression. ...In this study, we...demonstrate that CD38 overexpression resulted in growth suppression and apoptosis accompanied by cleavage of poly (ADP-ribose) polymerase 1 (PARP1). CD38 overexpression also dramatically reduced intracellular NAD+ levels and decreased mitochondrial respiration as measured by oxygen consumption rate. We further show that some but not all of these CD38-induced phenotypes could be rescued by exogenous NAM. Treatment of cells with NAM rescued CD38-induced apoptosis and mitochondrial stress but did not restore intracellular NAD+ levels. We also found that NAM demonstrated biphasic effect on mitochondria function, a finding that can be explained by the dual role of NAM as both a precursor of NAD+ and also as a suppressor of a number of NAD+-dependent enzymes...

Apr 8, 2022

Cancer - Leukemia - Gut Microbiome

Cell Death & Disease

Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia

ElMokh, Oussama


Antibiotic therapy down-modulating gut microbiota can restore the anti-cancer efficacy of APO866. Alternatively, NAphosphoribosyltransferase inhibition may restore anti-cancer activity of NAMPT inhibitors in the presence of gut microbiota and of NAM in the diet.

Apr 7, 2022

Cancer - NF1

Cell Death & Differentiation

Tumor growth of neurofibromin-deficient cells is driven by decreased respiration and hampered by NAD+ and SIRT3

Masgras, Ionica


Upon neurofibromin loss, hyperactivation of Ras/MEK/ERK signaling inhibits complex I, causing a decrease in the NAD+/NADH ratio and the ensuing SIRT3 repression. Raising the NAD+/NADH ratio via NDI1 expression has an antineoplastic effect through the enhancement of SIRT3 activity...These findings indicate that tumorigenic growth of NF1-related neoplasms can be impaired both by TRAP1 ablation and by SIRT3 re-activation. Combination of these two approaches reaches maximal efficacy when SIRT3 induction is achieved through a rise in NAD+ precursors...These observations point toward a bona fide tumor suppressor role for SIRT3, which is abrogated by respiratory complex I inhibition and the ensuing decrease of NAD+/NADH ratio in NF1-related tumor cells...We envision that enhancement of SIRT3 activity and replenishment of NAD+ levels result in a multifaceted metabolic rewiring, which can oppose NF1-related cancer growth by affecting multiple bioenergetic pathways.

NAD Research - Cancer / Chemo

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