title: Preventive effects of curcumin on the development of azoxymethane-induced colonic preneoplastic lesions in male C57BL/KsJ-db/db obese mice.
abstract: Obesity-related metabolic abnormalities include a state of chronic inflammation and adipocytokine imbalance, which increase the risk of colon cancer. Curcumin, a component of turmeric, exerts both cancer preventive and antiinflammatory properties. Curcumin is also expected to have the ability to reverse obesity-related metabolic derangements. The present study examined the effects of curcumin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice. Feeding with a diet containing 0.2% and 2.0% curcumin caused a significant reduction in the total number of colonic premalignant lesions compared with basal diet-fed mice. The expression levels of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 (COX-2) mRNAs on the colonic mucosa of AOM-treated mice were significantly decreased by curcumin administration. Dietary feeding with curcumin markedly activated AMP-activated kinase, decreased the expression of COX-2 protein, and inhibited nuclear factor-κB activity on the colonic mucosa of AOM-treated mice. Curcumin also increased the serum levels of adiponectin while conversely decreasing the serum levels of leptin and the weights of fat. In conclusion, curcumin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model, at least in part, by attenuating chronic inflammation and improving adipocytokine imbalance. Curcumin may be useful in the chemoprevention of colorectal carcinogenesis in obese individuals.
authors.affiliation: Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Daishi
authors.initials: D
authors.lastname: Terakura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Baba
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohno
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D003474:Curcumin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D015850:Interleukin-6 / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009765:Obesity / Q000150:complications*; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011494:Protein Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D016588:Anticarcinogenic Agents; D015850:Interleukin-6; D020738:Leptin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D003474:Curcumin; D001397:Azoxymethane