Comparative Study on The Preventive Effect of Saffron Carotenoids, Crocin and Crocetin, in NMU-Induced Breast Cancer in Rats

Objective: Crocin (Cro) and crocetin (Crt) are two widely known saffron carotenoids, which exert anticancer effects by different mechanisms. Here, we investigated and compared the preventive effect of Cro and Crt at the initiation and promotion stages of breast cancer induction in an animal model. Materials and Methods: In this experimental study, female Wistar albino rats were injected with three doses of N-methyl-N-nitrosourea (NMU). The preventive intervention was done at different times for the initiation and promotion stages. Thus, Cro/Crt was administered by gavage 20 days before, or one week after, the first NMU injection, for the prevention at the initiation or promotion stages respectively. The treatment was repeated every three days, and continued up to the end of experiment. Tumor appearance was checked by palpation and some parameters were determined after sacrifice. Results: Tumor volume, latency period, and tumor number were significantly decreased in the rat groups treated with both saffron carotenoids for prevention at both the initiation and promotion stages. Tumor incidence was 77% due to NMU injection, which was decreased to 45 and 33% (on average) after Cro and Crt administration, respectively. In addition, enkephaline degrading aminopeptidase (EDA) was decreased significantly in the ovaries of the animals, however, changes in the brain were not significant. Conclusion: Crt/Cro showed a significant protective effect against the NMU-induced breast cancer in rats. However, Crt was more effective than Cro and prevention at the initiation stage was more effective than at the promotion stage.