title: Chemoprevention of colorectal cancer by targeting obesity-related metabolic abnormalities.
abstract: Obesity and its related metabolic disorders, including insulin resistance and chronic inflammation, increase the risk of colorectal cancer (CRC). This observation suggests that the metabolic abnormalities associated with obesity can be effective targets for preventing the development of CRC in obese individuals. In recent years, many studies using obese and diabetic animal models have been conducted to investigate the chemoprevention of CRC using pharmaceutical or nutritional interventions. Pitavastatin, a medicine used to treat hyperlipidemia, prevents the development of obesity-related colorectal carcinogenesis by attenuating chronic inflammation. Anti-hypertensive medicines, such as captopril and telmisartan, also suppress the formation of colonic preneoplastic lesions in obese and diabetic mice. In addition, several phytochemicals, including green tea catechins, have been reported to improve metabolic disorders and prevent the development of various cancers, including CRC. Moreover, the administration of branched-chain amino acids, which improves protein malnutrition and prevents the progression of hepatic failure, is effective for suppressing obesity-related colon carcinogenesis, which is thought to be associated with improvements in insulin resistance. In the present article, we summarize the detailed relationship between metabolic abnormalities and the development of CRC. This review also outlines recent evidence, in particular drawing from basic and clinical examinations using either pharmaceutical or nutritional intervention that suggests that targeting metabolic alterations may be an effective strategy for preventing the development of CRC in obese individuals.
authors.affiliation: Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.affiliation: Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Araki
authors.affiliation: Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Yohei Shirakami, Mitsuru Seishima, Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002392:Catechin / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D009752:Nutritional Status; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D012307:Risk Factors; D040242:Risk Reduction Behavior; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D000959:Antihypertensive Agents; D000960:Hypolipidemic Agents; D002392:Catechin
keywords: Branched-chain amino acid; Chemoprevention; Colorectal cancer; Green tea catechin; Obesity
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