Abstract
BackgroundObesity and related metabolic abnormalities, including excess oxidative stress and chronic inflammation, are associated with colorectal carcinogenesis. Astaxanthin, a xanthophyll carotenoid found in aquatic animals, is known to possess antioxidant, anti-inflammatory, and antineoplastic properties. The present study examined the effects of astaxanthin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice.MethodMale db/db mice were administered 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) from 5 weeks of age and subsequently, from 1 week after the last injection of AOM, were fed a diet containing 200 ppm astaxanthin throughout the experiment (8 weeks).ResultThe development of colonic premalignant lesions, i.e., aberrant crypt foci and β-catenin accumulated crypts, was significantly inhibited in mice treated with astaxanthin than in mice fed the basal diet. Astaxanthin administration markedly reduced urinary levels of 8-OHdG and serum levels of d-ROMs, which are oxidative stress markers, while increasing the expression of mRNA for the antioxidant enzymes GPx1, SOD1, and CAT in the colonic mucosa of AOM-treated db/db mice. The expression levels of IL-1β, IL-6, F4/80, CCL2, and CXCL2 mRNA in the colonic mucosa of AOM-treated mice were significantly decreased by astaxanthin. Dietary feeding with astaxanthin also resulted in a reduction in the numbers of NF-κB- and PCNA-positive cells that were increased by AOM exposure, in the colonic epithelium.ConclusionThese findings suggest that astaxanthin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model by reducing oxidative stress, attenuating chronic inflammation, and inhibiting NF-κB activation and cell proliferation in the colonic mucosa. Astaxanthin, therefore, may be a potential candidate as a chemoprevention agent against colorectal carcinogenesis in obese individuals.
Highlights
Obesity and related metabolic abnormalities, including excess oxidative stress and chronic inflammation, are associated with colorectal carcinogenesis
Dietary feeding with astaxanthin resulted in a reduction in the numbers of Nuclear factor-κB (NF-κB)- and proliferating cell nuclear antigen (PCNA)-positive cells that were increased by AOM exposure, in the colonic epithelium. These findings suggest that astaxanthin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model by reducing oxidative stress, attenuating chronic inflammation, and inhibiting NF-κB activation and cell proliferation in the colonic mucosa
Recent studies have demonstrated that certain types of phytochemicals such as curcumin and (−)-epigallocatechin gallate inhibit the development of obesity-related colorectal carcinogenesis in mice by attenuating chronic inflammation [11,12]
Summary
Obesity and related metabolic abnormalities, including excess oxidative stress and chronic inflammation, are associated with colorectal carcinogenesis. Recent studies have demonstrated that certain types of phytochemicals such as curcumin and (−)-epigallocatechin gallate inhibit the development of obesity-related colorectal carcinogenesis in mice by attenuating chronic inflammation [11,12]. Administration of angiotensin-converting enzyme inhibitor suppresses the early phase of colorectal carcinogenesis in diabetic and hypertensive rats by attenuating inflammation and oxidative stress [13]. These reports suggest that targeting obesity-related metabolic abnormalities including chronic inflammation and oxidative stress using phytochemicals and specific agents is an effective strategy for preventing CRC development in obese individuals [3]
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