Crocetin and crocin from saffron in cancer chemotherapy and chemoprevention

Introduction: Cancer is a disorder which has a powerful impact on the quality life and life expectancy despite the increase in drugs and treatments available for cancer patients. Moreover, many new therapeutic options are known to have adverse reactions without any improvement in outcome than before. Nowadays, natural products or plant derivatives are used as chemoprevention drugs and chemotherapy is the new approach that uses specific cell premalignant transformation in the malignant form. Natural substances derived from plants, such as polyphenols, flavonoids, carotenoids, alkaloids and others, can be biologically active and have a wide spectrum of effects. The protective effects of Saffron carotenoids (crocin and crocetin) have been extensively studied mainly for their antioxidant properties, however, they have various other biological activities including tumor growth inhibition with the induction of cell death. Methods: The relevant information on Saffron and its carotenoids was collected from scientific databases (such as PubMed, Web of Science, Science Direct). To identify all published articles in relation to saffron, crocin and crocetin, in different types of cancer, no language restriction has been used. Results: To date, crossing the words saffron and cancer, approximately 150 articles can be found. If crossing is made between crocin and cancer, approximately 60 articles can be found. With the crossing between crocetin and cancer, the number is approximately 55, while between carotenoids and cancer, the number exceeds 16.000 reports. In all the papers published to date, there are evidences that saffron and its carotenoids exert chemopreventive activity through anti-oxidant activity, cancer cells apoptosis, inhibition of cell proliferation, enhancement of cell differentiation, modulation of cell cycle progression and cell growth, modulation of tumor metabolism, stimulation of cell-to-cell communication and immune modulation. Conclusion: Here, we have tried to offer an up-to-date overview of pre-clinical experimental investigations on the potential use of the main carotenoids of saffron in tumor models and focus the attention on the molecular mechanisms involved. Since ancient times herbs and spices have been used with strong roles on cultural heritage and on the appreciation of food and its links to health. Today, an important element of chemoprevention drug development is the new approach that uses specific natural products or plant's derivatives to suppress, reverse or prevent cell premalignant transformation in malignant form. It is also very important to note that suitable chemoprevention natural agents should have low or no toxicity, high efficacy, should be orally administrable, to have a known mechanism of action and low cost compared to the other chemotherapeutic agents. Natural products are composed of a wide spectrum of biologically active phytochemicals as polyphenols, flavonoids, carotenoids, alkaloid, and so on. Preclinical studies showed that carotenoids have potent antitumor effects both in vitro and in vivo, suggesting potential preventive and/or therapeutic roles. The potential cancer protective effect of carotenoids has been extensively studied mainly in relation to their antioxidant properties, but carotenoids (β-carotene, lycopene, lutein and zeaxantin, crocin and crocetin) have several other biological activities which involve multiple mechanisms promoting the inhibition of malignant tumor growth and the induction of apoptosis. Saffron, the dry stigmas of the Crocus sativus L., is an important source of carotenoids and has been used in traditional medicine in various parts of the world. The present review provides an updated overview of experimental in vitro and in vivo investigations on the potential use of saffron's carotenoids: crocin and crocetin in cancer therapy and chemoprevention trials.