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A combination of resveratrol and melatonin exerts chemopreventive effects in N-methyl-N-nitrosourea-induced rat mammary carcinogenesis

Kisková, Teréziaa; Ekmekcioglu, Cemc,f; Garajová, Miroslavaa; Orendáš, Petera; Bojková, Biankaa; Bobrov, Nikitab; Jäger, Waltere; Kassayová, Monikaa; Thalhammer, Theresiad

European Journal of Cancer Prevention: March 2012 - Volume 21 - Issue 2 - p 163–170
doi: 10.1097/CEJ.0b013e32834c9c0f
Research Paper: Breast cancer

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.

aDepartment of Animal Physiology, Institute of Biology and Ecology

bDepartment of Forensic Medicine, Faculty of Medicine, P.J. Šafárik University, Košice, Slovak Republic

cInstitute of Physiology, Center for Physiology and Pharmacology

dDepartment of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna

eDepartment of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna

fLudwig Boltzmann Institute, Cluster for Rheumatology, Balneology and Rehabilitation, A-1090 Vienna, Austria

Correspondence to Dr Cem Ekmekcioglu, MD, Institute of Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria Tel: +43 1 4277 62114; fax: +43 1 4277 62199; e-mail:

Received May 18, 2011

Accepted July 16, 2011

© 2012 Lippincott Williams & Wilkins, Inc.