title: Anticarcinogenic activity of meso-zeaxanthin in rodents and its possible mechanism of action.
abstract: Anticarcinogenic activity of meso-zeaxanthin (MZ), a xanthophyll carotenoid with profound antioxidant activity, was evaluated against 3-methylcholanthrene (3-MC)-induced sarcoma in mice. Oral administration of MZ at different doses significantly increased tumor latency period. In 3-MC control group, animals started developing sarcoma on 6th week. However animals treated with 3-MC and MZ (50 and 250 mg/kg b.wt) started developing sarcoma only on 15th and 18th week, respectively. Survival of tumor-bearing mice was significantly increased by MZ treatment. Animals in 3-MC control group started dying due to tumor burden from 8th week. All animals treated with MZ (50 and 250 mg/kg b.wt) along with 3-MC were found to be alive even after 16 and 20 wk, respectively. Oral administration of MZ inhibited different CYP450 isoenzymes like CYP1A1 (PROD), CYP1A2 (MROD), and CYP2B1/2 (EROD), which are involved in carcinogen metabolism in a dose-dependent manner. Moreover, levels of phase II enzymes like UDP-glucuronyl transferase and glutathione-S-transferase, which are involved in detoxification of carcinogens, were significantly increased by MZ treatment. Results indicated that mode of action of MZ may be through inhibition of carcinogen activation coupled with enhancement of detoxification process. MZ may also inhibit promotion phases of carcinogenesis by its antioxidant activity.
authors.affiliation: Amala Cancer Research Centre, Kerala, India.
authors.forename: Alikkunjhi Pararikkal
authors.initials: AP
authors.lastname: Firdous
authors.forename: Edakkadath Raghavan
authors.initials: ER
authors.lastname: Sindhu
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Ramnath
authors.forename: Ramadasan
authors.initials: R
authors.lastname: Kuttan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019362:Cytochrome P-450 CYP2B1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced / Q000188:drug therapy; D024341:Xanthophylls / Q000494:pharmacology*; D065146:Zeaxanthins
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D024341:Xanthophylls; D065146:Zeaxanthins; C584722:meso-zeaxanthin; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase