J. Pineal Res. 2007; 43:270–275
2007 The Authors Journal compilation 2007 Blackwell Munksgaard
Doi:10.1111/j.1600-079X.2007.00472.x
Journal of Pineal Research
Beneficial properties of melatonin in an experimental model of pancreatic cancer Abstract: Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin has antioxidant activity and prevents experimental genotoxicity. However, the effect of melatonin in pancreatic cancer has not been tested. Pancreatic carcinogenesis was induced by N-nitrosobis (2-oxopropyl)amine (BOP) in Syrian hamsters. Melatonin was administered during the BOPinduction phase (12 wk) and/or following the postinduction phase (12 wk). Different parameters of oxidative stress including lipid peroxides (LPO) and antioxidants (superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase) were determined in pancreatic tissue. Also, the presence of atypical hyperplasia (AH), well and moderately differentiated adenomacarcinoma (ADC-WD and ADC-MD, respectively) were studied. The administration of BOP induced an intense oxidative stress and ADC induction in the pancreas. The administration of melatonin during the induction or postinduction phase reduced LPO and improved the antioxidant status, as well as drastically reducing the presence of ADC but some AH remained. In conclusion, treatment with melatonin reduced oxidative damage and cancer nodules induced by BOP in the pancreas.
Juan F. Ruiz-Rabelo1, Reyes Va´zquez1, Marı´a D. Perea1, Adolfo Cruz1, Raul Gonza´lez2, Ana Romero3, Marı´a C. Mun˜ozVillanueva2, Isaac Tu´nez4, Pedro Montilla4, Jordi Muntane´2 and Francisco Javier Padillo1 1
Department of General Surgery; 2Research Unit and 3Pathology Department, Reina Sofia University Hospital, Cordoba; 4Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Cordoba, Cordoba, Spain
Key words: lipid peroxidation, melatonin, oxidative stress, pancreatic cancer, Syrian hamster Abbreviations: ADC, Adenocarcinoma; BOP, N-nitrosobis(2-oxopropyl)amine; CAT, catalase; GSH, reduced glutathione; GSH-Px, glutathione peroxidase; LPO, lipid peroxidation products; MDA + 4-HDA, malondialdehyde + 4-hydroxyalkenals; MEL, melatonin; ADC-MD, moderated differentiated adenocarcinoma; SOD, superoxide dismutase; ADC-WD, well differentiated adenocarcinoma. Address reprint requests to Francisco J. Padillo, Department of Surgery, Hospital Reina Sofia, Avenida Menendez Pidal s/n, 14004-Cordoba, Spain. E-mail:
[email protected] Received March 24, 2007; accepted May 29, 2007.
Introduction Tumors of the pancreas are the fourth most common cause of death because of cancer in Europe, with a constant incidence and mortality rates per year [1]. Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, the disease remains a clinical challenge. Surgery is the only curative therapeutic option, but
