Nocturnal resveratrol administration inhibits chemically induced breast cancer formation in rats.

ABSTRACT

Resveratrol (RES) is well known natural polyphenol with proven antioxidant, antiinflammatory and anticarcinogenic properties. Since mode of application may be important for cancer-preventive effects of RES, the aim of this study was to evaluate a possible delay in the initiation and progression of chemically induced mammary carcinogenesis in female Sprague-Dawley rats after the nocturnal administration of RES. Application of a high dose of RES (100 mg/kg body weight), starting 2 weeks before the first N-methyl-N-nitrosourea dose (NMU) (50 mg/kg body weight), reduced tumor incidence and markedly prolonged latency period (P < 0.01) in the NMU + RES group in comparison to NMU tumor bearing animals. In addition, the tumor volume decreased significantly (P < 0.05) together with tumor frequency (P < 0.05). We also observed that food but not water intake was significantly reduced by 17% between weeks 4 and 12 in the NMU + RES group leading to a pronounced reduction in the body mass of about 25% as compared to untreated controls. In addition to direct effects of RES in tumor tissues, this polyphenol did also improve metabolic functions in RES-treated animals since it normalizes hypoproteinemia and urea levels and increases the number of lymphocytes when compared with NMU. Higher level of reactive oxygen species (ROS) in leukocytes and the elevation of proinflammatory plasma cytokines IL-1 and IL-2 may contribute to the observed reduction in tumor development. These results indicate for the first time that nocturnal administration of a high dose of RES significantly affects tumor development in vivo. Therefore, we conclude that RES is a promising candidate for cancer chemoprevention. However, it should be noted that the mode of application might significantly affect RES ability to fight cancer.