Studies on the chemopreventive potential of melatonin on 7,12-dimethylbenz(a)anthracene induced mammary carcinogenesis in rats

Chemoprevention using drugs is a promising approach to control the mortality and occurrence of cancer that accounts for millions of death worldwide. Melatonin (N-acetyl-5-methoxytryptamine), a hormone of the pineal gland produced from the amino acid tryptophan in minute quantities has been known to be a chemoprventive, anticancer agent in vitro and in vivo studies. DMBA (7, 12-dimethylbenz(a)anthracene) has been shown to act via generation of reactive oxygen species (ROS) as tumor promoter and also involved in the generation of free radicals. Many natural and synthetic compounds exhibit potent cancer chemopreventive property as observed in the last few decades. Most of them are known to exert their effects by quenching reactive oxygen, inhibiting lipid peroxidation. DMBA is a potent carcinogenic agent that induces mammary cancer. Here we evaluate the chemopreventive potential of melatonin on experimental animal models, female albino Wistar rats were randomized into four groups. Group I animals served as control without any treatment. Group II animals received a dose of 5mg/kg body weight of DMBA orally at weekly intervals for one month. Group III animals received a daily intraperitoneal administration of melatonin 5mg/ml per animals for 15 days prior to the first oral administration of DMBA and continued for a month and Group IV animals received a daily intraperitoneal administration of melatonin 5mg/ml beginning the next day after first DMBA administration for one month. At the end of the experiment the rats were killed, blood, liver, kidney and mammary tissues were taken for biochemical and histological studies. As a marker for liver function, the activity of gamma glutamyl transpeptidase (GGT) was measured in the serum. To assess the lipid peroxidation and the antioxidant status in tissues, the levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), ascorbic acid (vitamin C) and aα-tocopherol (vitamin E) were measured. DMBA administration inhibited body weight and enhanced macroscopically detectable tumors with a increase in serum GGT and TBARS levels. DMBA treatment decreased both enzymic and non-enzymic antioxidant status. Melatonin administration significantly curtailed tumor development and counteracted all the biochemical effects. This indicates that melatonin should be considered as an adjuvant drug in the treatment of neoplastic disease.