252 NEOPLASMA 56, 3, 2009 Celecoxib and melatonin in prevention of female rat mammary carcinogenesis P. ORENDAS 1 , M. KASSAYOVA 1 , K. KAJO 2 , I. AHLERS 1 *, P. KUBATKA 3 , B. BOJKOVA 1 , M. PEC 3 , E. AHLERSOVA 1 1 Department of Animal Physiology, Institute of Biology and Ecology, Faculty of Science, P. J. Šafárik University, Moyzesova 11 , 040 01 Košice, Slovak Republic, * e-mail: iahlers@upjs.sk; 2  Department of Pathological Anatomy, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic; 3  Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic Received July 7, 2008 The present experiment aims to evaluate tumor suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2) celecoxib (Celebrex, Pfizer) administered alone and in combination with melatonin in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley female rats. Celecoxib was administered daily at a concentration of 1.666 g/kg diet to two groups during 20 weeks (starting a week before first NMU application). A combination of celecoxib and melatonin applied in drinking water (20 μg/ml drinking water), daily from 15:00 to 08:00 hours was administered to the second group. The anticarcinogenic effects of chemopreventive drugs were compared with control (NMU) animals. Celecoxib administration decreased mammary tumor incidence (by 24%), while combination of celecoxib and melatonin decreased tumor incidence even more significantly (-30%). Significant decrease in tumor frequency per group was recorded in both groups with chemoprevention: celecoxib alone (-54%) and combination of celecoxib and melatonin (-64%). Celecoxib significantly influenced tumor frequency per animal in the group with combination of both protective substances (-52%). Celecoxib administration resulted in prolonged latency by 3%, and by 13% in the group with combination of both protective substances. These results confirm preventive effects of celecoxib in induced rat mammary carcinogenesis. The administration of isolated MEL had only lesser effect, but in the combination with CELE revealed some potentiating influence in mammary carcinogenesis inhibition. The present study is the first to prove efficacy of the above-mentioned celecoxib and melatonin intake. Our results point to the need for a deeper analysis of coxib efficacy in human carcinogenesis. Key words: mammary carcinogenesis, female rats, celecoxib, melatonin * Corresponding author Mammary gland cancer presents a serious health issue worldwide. It is one of the most frequent malignancies in women in industrialised countries and it is the second most frequent cause of death in women with cancer. Annually, breast cancer is diagnosed in 40 000 women only in the UK [1]. Apart from maintaining a healthy lifestyle, chemoprevention is efficient to combat mammary gland cancer. Non-steroidal antiinflammatory drugs (NSAIDs) have been found to have chemopreventive effects. NSAIDs belong to the most frequently used drugs worldwide; with as many as 20 to 30 % of the popu- lation in the developed countries taking prescribed forms of these agents [2]. NSAIDs are often used in the treatment of rheumatic diseases, to alleviate pain and functional impairment. Several retrospective clinical studies aimed at a long-term application of various NSAIDs reported significant decrease in the incidence of colon cancer [3], mammary gland cancer [4], prostate [5] and lung cancer [6]. The studies with labora- tory animals proved chemopreventive effect of NSAIDs in various types of neoplasia, including mammary gland can- cer. Dietary ibuprofen and celecoxib administration (one week before carcinogen application to the end of the experiment – 105 days after the application of 7,12-dimethylbenzanthracene – DMBA) in mammary tumorigenesis decreased tumor inci- dence, tumor frequency and tumor volume in female rats; celecoxib proved to be more efficient [7]. Nimesulide applied in a high-fat diet in rat mammary carcinogenesis induced by 2-amino-1-methyl-6-fenylimidazol (4,5-b) pyridine reduced tumor incidence, frequency and volume as opposed to the group without nimesulide [8].