Inhibitory effects of astaxanthin on azoxymethane-induced colonic preneoplastic lesions in C57/BL/KsJ-db/db mice

BMC Gastroenterol. 2014 Dec 17;14:212. doi: 10.1186/s12876-014-0212-z.


Background: Obesity 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.

Method: Male 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).

Result: The 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.

Conclusion: 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. Astaxanthin, therefore, may be a potential candidate as a chemoprevention agent against colorectal carcinogenesis in obese individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Azoxymethane
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control*
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Obesity / complications*
  • Oxidative Stress / drug effects
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / prevention & control*
  • Xanthophylls / pharmacology
  • Xanthophylls / therapeutic use
  • beta Catenin / metabolism


  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Inflammation Mediators
  • NF-kappa B
  • Xanthophylls
  • beta Catenin
  • astaxanthine
  • Azoxymethane