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A lipophilic statin, pitavastatin, suppresses inflammation‐associated mouse colon carcinogenesis
Author(s) -
Yasui Yumiko,
Suzuki Rikako,
Miyamoto Shingo,
Tsukamoto Tetsuya,
Sugie Shigeyuki,
Kohno Hiroyuki,
Tanaka Takuji
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22976
Subject(s) - pitavastatin , inflammation , statin , medicine , carcinogenesis , hydroxymethylglutaryl coa reductase inhibitors , colorectal cancer , cancer research , pharmacology , gastroenterology , cancer
Abstract 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. © 2007 Wiley‐Liss, Inc.