A combination of resveratrol and melatonin exerts chemopreventive effects in N-methyl-N-nitrosourea-induced rat mammary carcinogenesis

Abstract

The neurohormone melatonin is primarily involved in the regulation of circadian rhythms, but also acts as an antioxidant and anticarcinogenic agent, especially in breast cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a widely known polyphenolic agent from red wine, which has been shown to exert antioxidant, anti-inflammatory and anticarcinogenic effects. The objective of this study was therefore to investigate the effects of melatonin in combination with resveratrol in a rat model of experimental mammary carcinogenesis. Female Sprague-Dawley rats aged 31 days were used in the experiment. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea (NMU), which was administered in two intraperitoneal doses (50 mg/kg of body weight). Chemoprevention with resveratrol and melatonin started 2 weeks before the first dose of NMU and lasted until the end of the experiment. The basic parameters evaluated were: tumour incidence, latency period, tumour frequency per group and tumour volume. In addition, oestrogen receptors ERα and ERß, melatonin receptor MT1, proliferating cell nuclear antigen and vascular endothelial growth factor were determined by immunohistochemical staining. The combination of resveratrol and melatonin reduced tumour incidence by approximately 17% and significantly decreased the quantity of invasive and in-situ carcinomas. Food intake declined in the second and seventh weeks after the administration of carcinogen. Resveratrol in combination with melatonin returned food intake to the level of intact controls. Resveratrol in combination with melatonin has some protective effects on NMU-induced rodent breast cancer. Further studies are necessary to confirm these effects of this promising combination.

Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases

“…The treatment reduced tumor incidence, significantly decreased invasive and in situ carcinomas and prevented the food intake reduction resulting from carcinogen application in rats (Kisková et al, 2012). However, the reason for the superior effect of resveratrol/melatonin remains unknown.…”

Resveratrol‐based combinatorial strategies for cancer management

“…Some recent studies have also evaluated the combinatorial effects of resveratrol with other naturally occurring and chemotherapeutic agents, suggesting that resveratrol can improve the efficacy of other agents. [2][3][4][5][6][7][8] Indeed, the strategy of using resveratrol in combination with other agents, particularly with chemotherapeutic modalities, may hold clinical promise for cancer management. However, evidence-based scientific evaluations in appropriate models are needed to show the efficacy of resveratrol in combination with other agents.…”

Rosiglitazone Shows Partial Oncostatic Effect in Rat Mammary Carcinogenesis

“…It was reported that estrogen receptor β (ERβ) can inhibit ligand-mediated PPARγ-transcriptional activity and subsequently block PPARγ-induced gene expression. As we reported before, NMU-induced tumors in Sprague-Dawley rats show strong positivity for both ERα and ERβ [55] which can interfere with thiazolidinedione activity. Neither higher nor lower ROS dose significantly altered tumor growth with the exception of decreased tumor frequency per group after higher ROS dose (by 44%).…”