Nicotinamide mononucleotide protects STAT1 from oxidative stress-induced degradation to prevent colorectal tumorigenesis.

Li T, Luo C, Liu Z, Li J, Han M, Zhang R, Chen Y, Deng H

MedComm21 Nov 2024Cited by 4 (Europe PMC)

PMID39575303PMCIDPMC11581775DOI10.1002/mco2.70006PepBankPUB-39575303

Summary

Colitis, accompanied by the accumulation of reactive oxygen species (ROS) in the intestinal tract, is a risk factor for colorectal cancer (CRC). Our previous studies indicate that nicotinamide mononucleotide (NMN) replenishment reduces chronic inflammation. In this study, we confirm that NMN supplementation reduces inflammatory cytokine levels and oxidative tissue damage in an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) model. Mice treated with NMN developed fewer colon tumors than untreated animals under the same AOM/DSS treatment conditions. Quantitative proteomic analysis revealed a decrease in signal transducer and activator of transcription 1 (STAT1) expression in the CAC model. We demonstrate that STAT1 overexpression induces G1 arrest by downregulating CDK6 expression and suppressing tumor cell proliferation and migration. Of note, H₂O₂ induced trioxidation of the STAT1 protein and promoted its degradation, which was partially reversed by NMN supplementation. Upon H₂O₂ treatment, Cys155 in STAT1 was oxidized to sulfonic acid, whereas the mutation of Cys155 to alanine abolished ROS-mediated STAT1 degradation. These results indicate that oxidative stress induces STAT1 degradation in tumor cells and possibly in CAC tissues, whereas supplementation with NMN protects STAT1 from oxidation-induced degradation and prevents tumorigenesis. This study provides experimental evidence for the development of NMN-mediated chemoprevention strategies for CRC.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In the AOM/DSS cancer model, NMN reduced inflammatory cytokine levels.
In plain wordsIn mice with chemically induced colon cancer, NMN reduced inflammatory cytokines compared with the same treatment without NMN.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseInflammatory cytokine levels
Study
mousen: not reported in source
AOM/DSS colitis-associated cancer model
Comparator
Same AOM/DSS treatment without NMN
Outcome group
Inflammation markers · Cancer
Studied dose
Dose not stated
Source sentences
Summary
In this study, we confirm that NMN supplementation reduces inflammatory cytokine levels and oxidative tissue damage in an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) model.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice treated with NMN developed fewer colon tumors than untreated animals under the same AOM/DSS treatment conditions.
Show in the study text Report a problemFND-3957530301
02AnimalAnimal study (in vivo)Efficacy outcome
In the AOM/DSS cancer model, NMN reduced oxidative tissue damage.
In plain wordsIn mice with chemically induced colon cancer, NMN reduced oxidative tissue damage compared with the same treatment without NMN.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseOxidative tissue damage
Study
mousen: not reported in source
AOM/DSS colitis-associated cancer model
Comparator
Same AOM/DSS treatment without NMN
Outcome group
Oxidative stress · Cancer
Studied dose
Dose not stated
Source sentences
Summary
In this study, we confirm that NMN supplementation reduces inflammatory cytokine levels and oxidative tissue damage in an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) model.
1 context sentence(design, population, supporting numbers)
Summary · context
Mice treated with NMN developed fewer colon tumors than untreated animals under the same AOM/DSS treatment conditions.
Show in the study text Report a problemFND-3957530302
03AnimalAnimal study (in vivo)Efficacy outcome
In AOM/DSS-treated mice, NMN reduced colon tumor number compared with untreated animals under the same treatment conditions.
In plain wordsIn mice, NMN reduced colon tumor numbers compared with the same cancer-inducing treatment without NMN.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseColon tumor number
Study
mousen: not reported in source
AOM/DSS colitis-associated cancer model
Comparator
Same AOM/DSS treatment without NMN
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated
Source sentences
Summary
Mice treated with NMN developed fewer colon tumors than untreated animals under the same AOM/DSS treatment conditions.
Show in the study text Report a problemFND-3957530303
04LabIn vitro (cells)Mechanism
In oxidative stress experiments, NMN partially reversed hydrogen peroxide-induced STAT1 degradation.
In plain wordsIn lab tests, NMN partly reversed STAT1 protein degradation compared with hydrogen peroxide alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseSTAT1 degradation
Study
n: not reported in source
Oxidative stress experiment
Comparator
Hydrogen peroxide alone
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated
Source sentences
Summary
Of note, H₂O₂ induced trioxidation of the STAT1 protein and promoted its degradation, which was partially reversed by NMN supplementation.
Show in the study text Report a problemFND-3957530304

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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