title: Suppressive effects of the NADPH oxidase inhibitor apocynin on intestinal tumorigenesis in obese KK-A(y) and Apc mutant Min mice.
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.
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors: Masami
authors: M
authors: Komiya
authors: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan.
authors: Gen
authors: G
authors: Fujii
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors: Shingo
authors: S
authors: Miyamoto
authors: Division of Central Animal Division, National Cancer Center Research Institute, Tokyo, Japan.
authors: Mami
authors: M
authors: Takahashi
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors: Rikako
authors: R
authors: Ishigamori
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.|Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Japan.
authors: Wakana
authors: W
authors: Onuma
authors: Division of Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan.
authors: Kousuke
authors: K
authors: Ishino
authors: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan.
authors: Yukari
authors: Y
authors: Totsuka
authors: Division of Molecular Biology, Nagasaki International University, Nagasaki, Japan.
authors: Kyoko
authors: K
authors: Fujimoto
authors: Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.|Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan.
authors: Michihiro
authors: M
authors: Mutoh
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D009765:Obesity; D060888:Real-Time Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: Apc mutant mice; KK-Ay mice; NADPH oxidase; apocynin; iNOS