astaxanthine and Precancerous-Conditions

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.. 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).. 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.. 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.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Azoxymethane; beta Catenin; Cell Proliferation; Colonic Neoplasms; Inflammation Mediators; Intestinal Mucosa; Male; Mice, Inbred C57BL; NF-kappa B; Obesity; Oxidative Stress; Precancerous Conditions; Xanthophylls

Colon cancer is one of the major causes of cancer mortality worldwide. Several carotenoids with antioxidant properties are reported for their chemopreventive nature. In this study, we have evaluated the chemopreventive efficacy of astaxanthin on lipid peroxidation, antioxidant status, total number of aberrant crypt foci (ACF), and cell proliferation in 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis using a rat model. DMH was induced subcutaneously at a dosage of 40 mg/kg body weight, twice a week for 2 weeks. Astaxanthin was administered before and after the DMH induction, orally at a concentration of 15 mg/kg body weight throughout the experimental period. At the end of 16 weeks, pre-treatment with astaxanthin markedly reduced the degree of histological lesions, ACF development and also lowered the number of argyrophilic nucleolar organizer regions. Our results also showed the decreased levels of colon enzymic and non-enzymic antioxidants and increased levels of lipid peroxidation marker levels in DMH-induced rats, which were significantly reversed on astaxanthin administration. In conclusion, the results of this study suggest that astaxanthin has an affirmative and beneficial effect against chemically induced colonic pre-neoplastic progression in rats induced by DMH.

Topics: 1,2-Dimethylhydrazine; Administration, Oral; Animals; Antigens, Nuclear; Antioxidants; Cell Proliferation; Colon; Colonic Neoplasms; Disease Models, Animal; Lipid Peroxidation; Male; Precancerous Conditions; Rats; Rats, Wistar; Xanthophylls

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) on oral carcinogenesis induced by 4-nitroquinoline 1-oxide (4-NQO) was investigated in male F344 rats. Rats were given 20 ppm of 4-NQO in their drinking water for 8 weeks to induce oral neoplasms or preneoplasms. Animals were fed diets containing 100 ppm AX or CX during the initiation or postinitiation phase of 4-NQO-induced oral carcinogenesis. The others contained the groups of rats treated with AX or CX alone and untreated. At the end of the study (week 32), the incidences of preneoplastic lesions and neoplasms in the oral cavity of rats treated with 4-NQO and AX or CX were significantly smaller than those of rats given 4-NQO alone (P < 0.001). In particular, no oral neoplasms developed in rats fed AX and CX during the 4-NQO exposure and in those given CX after the 4-NQO administration. Similarly, the incidences of oral preneoplastic lesions (hyperplasia and dysplasia) in rats treated with 4-NQO and AX or CX were significantly smaller than that of the 4-NQO-alone group (P < 0.05). In addition to such tumor inhibitory potential, dietary exposure of AX or CX decreased cell proliferation activity in the nonlesional squamous epithelium exposed to 4-NQO as revealed by measuring the silver-stained nucleolar organizer regions protein number/nucleus and 5'-bromodeoxyuridine-labeling index. Also, dietary AX and CX could reduce polyamine levels of oral mucosal tissues exposed to 4-NQO. These results indicate that AX and CX are possible chemopreventers for oral carcinogenesis, and such effects may be partly due to suppression of cell proliferation.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Bromodeoxyuridine; Canthaxanthin; Carotenoids; Male; Mouth Neoplasms; Nucleolus Organizer Region; Precancerous Conditions; Rats; Rats, Inbred F344; Xanthophylls

The chemopreventive effects of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX), on urinary bladder carcinogenesis induced by N-butyl-N(4-hydroxybutyl)nitrosamine (OH-BBN) was investigated in male ICR mice. Mice were given 250 p.p.m. OH-BBN in drinking water for 20 weeks and after a 1 week interval with tap water, water containing AX or CX at a concentration of 50 p.p.m. was administered during subsequent 20 weeks. Other groups of mice were treated with AX or CX alone or untreated. At the end of the study (week 41), the incidences of preneoplastic lesions and neoplasms in the bladder of mice treated with OH-BBN and AX or CX were smaller than those of mice given OH-BBN. In particular, AX administration after OH-BBN exposure significantly reduced the incidence of bladder cancer (transitional cell carcinoma) (P < 0.003). However, the inhibition of the frequencies of such lesions in mice treated with OH-BBN and CX was not significant. Treatment with AX or CX also decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), a new index of cell proliferation, in the transitional epithelium exposed to OH-BBN. Preneoplasms and neoplasms induced by OH-BBN, and the antiproliferative potential, was greater for AX than CX. These results indicate that AX is a possible chemopreventive agent for bladder carcinogenesis and such an effect of AX may be partly due to suppression of cell proliferation.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Body Weight; Butylhydroxybutylnitrosamine; Canthaxanthin; Carotenoids; Liver; Male; Mice; Mice, Inbred ICR; Nucleolus Organizer Region; Organ Size; Precancerous Conditions; Silver Staining; Urinary Bladder Neoplasms; Xanthophylls