A lipophilic statin, pitavastatin, suppresses inflammation-associated mouse colon carcinogenesis.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are known to modulate carcinogenesis. In this study, we investigated whether a lipophilic HMG-CoA reductase inhibitor pitavastatin suppresses inflammation-related mouse colon carcinogenesis. Male CD-1 (ICR) mice were initiated with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and promoted by 2% (w/v) dextran sodium sulfate (DSS) in drinking water for 7 days. The experimental diets containing pitavastatin at 2 dose levels (1 and 10 ppm) were fed to male CD-1 (ICR) mice for 17 weeks, staring 1 week after the cessation of DSS exposure. The effects of dietary pitavastatin on colonic tumor development were assessed at Weeks 5, 10 and 20. Feeding with pitavastatin at both doses significantly inhibited the multiplicity of colonic adenocarcinoma at Week 20. Furthermore, the treatment significantly lowered the positive rates of proliferating cell nuclear antigen and increased the apoptotic index in the colonic epithelial malignancies. The treatment also reduced nitrotyrosine-positivity in the colonic mucosa. Our findings thus show that pitavastatin is effective in inhibiting colitis-related colon carcinogenesis through modulation of mucosal inflammation, oxidative/nitrosative stress, and cell proliferation.
Department of Oncologic Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Yumiko
Y
Yasui
Rikako
R
Suzuki
Shingo
S
Miyamoto
Tetsuya
T
Tsukamoto
Shigeyuki
S
Sugie
Hiroyuki
H
Kohno
Takuji
T
Tanaka
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004277:DNA, Single-Stranded / Q000235:genetics; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004277:DNA, Single-Stranded; D018809:Proliferating Cell Nuclear Antigen; D011804:Quinolines; D014280:Triglycerides; C002744:3-nitrotyrosine; D014443:Tyrosine; D002784:Cholesterol; C108475:pitavastatin