Celecoxib and melatonin in prevention of female rat mammary carcinogenesis
Abstract:
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.