title: A combination of resveratrol and melatonin exerts chemopreventive effects in N-methyl-N-nitrosourea-induced rat mammary carcinogenesis.
abstract: The neurohormone melatonin is primarily involved in the regulation of circadian rhythms, but also acts as an antioxidant and anticarcinogenic agent, especially in breast cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a widely known polyphenolic agent from red wine, which has been shown to exert antioxidant, anti-inflammatory and anticarcinogenic effects. The objective of this study was therefore to investigate the effects of melatonin in combination with resveratrol in a rat model of experimental mammary carcinogenesis. Female Sprague-Dawley rats aged 31 days were used in the experiment. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea (NMU), which was administered in two intraperitoneal doses (50 mg/kg of body weight). Chemoprevention with resveratrol and melatonin started 2 weeks before the first dose of NMU and lasted until the end of the experiment. The basic parameters evaluated were: tumour incidence, latency period, tumour frequency per group and tumour volume. In addition, oestrogen receptors ERα and ERß, melatonin receptor MT1, proliferating cell nuclear antigen and vascular endothelial growth factor were determined by immunohistochemical staining. The combination of resveratrol and melatonin reduced tumour incidence by approximately 17% and significantly decreased the quantity of invasive and in-situ carcinomas. Food intake declined in the second and seventh weeks after the administration of carcinogen. Resveratrol in combination with melatonin returned food intake to the level of intact controls. Resveratrol in combination with melatonin has some protective effects on NMU-induced rodent breast cancer. Further studies are necessary to confirm these effects of this promising combination.
authors: Institute of Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
authors: Terézia
authors: T
authors: Kisková
authors: Cem
authors: C
authors: Ekmekcioglu
authors: Miroslava
authors: M
authors: Garajová
authors: Peter
authors: P
authors: Orendáš
authors: Bianka
authors: B
authors: Bojková
authors: Nikita
authors: N
authors: Bobrov
authors: Walter
authors: W
authors: Jäger
authors: Monika
authors: M
authors: Kassayová
authors: Theresia
authors: T
authors: Thalhammer
mesh_terms: D000465:Algorithms; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002273:Carcinogens; D002277:Carcinoma / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D018890:Chemoprevention / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008550:Melatonin / Q000008:administration & dosage* / Q000097:blood; D008770:Methylnitrosourea; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D002273:Carcinogens; D047628:Estrogen Receptor alpha; D018809:Proliferating Cell Nuclear Antigen; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D008770:Methylnitrosourea; D008550:Melatonin; D000077185:Resveratrol