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Suppressive effects of the NADPH oxidase inhibitor apocynin on intestinal tumorigenesis in obese KK‐A y and Apc mutant Min mice
- Source :
- Cancer Science
- Publication Year :
- 2015
- Publisher :
- John Wiley and Sons Inc., 2015.
-
Abstract
- Obesity is a risk factor for colorectal cancer. The accumulation of abdominal fat tissue causes abundant reactive oxygen species production through the activation of NADPH oxidase due to excessive insulin stimulation. The enzyme NADPH oxidase catalyzes the production of reactive oxygen species and evokes the initiation and progression of tumorigenesis. Apocynin is an NADPH oxidase inhibitor that blocks the formation of the NADPH oxidase complex (active form). In this study, we investigated the effects of apocynin on the development of azoxymethane-induced colonic aberrant crypt foci in obese KK-A(y) mice and on the development of intestinal polyps in Apc mutant Min mice. Six-week-old KK-A(y) mice were injected with azoxymethane (200 μg/mouse once per week for 3 weeks) and given 250 mg/L apocynin or 500 mg/L apocynin in their drinking water for 7 weeks. Six-week-old Min mice were also treated with 500 mg/L apocynin for 6 weeks. Treatment with apocynin reduced the number of colorectal aberrant crypt foci in KK-A(y) mice by 21% and the number of intestinal polyps in Min mice by 40% compared with untreated mice. Both groups of mice tended to show improved oxidation of serum low-density lipoprotein and 8-oxo-2'-deoxyguanosine adducts in their adipose tissues. In addition, the inducible nitric oxide synthase mRNA levels in polyp tissues decreased. Moreover, apocynin was shown to suppress nuclear factor-κB transcriptional activity in vitro. These results suggest that apocynin and other NADPH oxidase inhibitors may be effective colorectal cancer chemopreventive agents.
- Subjects :
- Male
Cancer Research
medicine.medical_specialty
Carcinogenesis
Adipose tissue
Antineoplastic Agents
Real-Time Polymerase Chain Reaction
chemistry.chemical_compound
Mice
NADPH oxidase complex
apocynin
Tandem Mass Spectrometry
Internal medicine
Cell Line, Tumor
medicine
Animals
Humans
Obesity
Enzyme Inhibitors
chemistry.chemical_classification
Reactive oxygen species
NADPH oxidase
biology
Azoxymethane
Apc mutant mice
Acetophenones
NADPH Oxidases
General Medicine
Original Articles
Immunohistochemistry
Mice, Mutant Strains
Nitric oxide synthase
iNOS
Disease Models, Animal
Endocrinology
Oncology
chemistry
Apocynin
biology.protein
Original Article
Female
Colorectal Neoplasms
Aberrant crypt foci
KK‐Ay mice
Chromatography, Liquid
Subjects
Details
- Language :
- English
- ISSN :
- 13497006 and 13479032
- Volume :
- 106
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....a4c20faef23b75afa21b05a7f8e5000f