ReviewCrocus sativus a natural food coloring and flavoring has potent anti-tumor properties
Graphical abstract
Schematic representation of Crocus sativus-mediated protective responses in cancer pathology
Introduction
Saffron is the dried stigmas of Crocus sativus L., and is a highly valued agricultural and pharmaceutical spice that is used exclusively for cooking purposes to give flavor, color and aroma to food (Sampathu et al., 1984). This member of the Iridaceae family originated in the Middle East but is now cultivated in different countries with very different climatic conditions (Xue, 1982); however, optimal climatic conditions are rainy autumns, mild winters and warm summers (Fernández, 2004, Mollafilabi, 2003). Even though it has been reported that saffron can tolerate temperatures as low as −18 °C (Mollafilabi, 2003) and as high as 40 °C (Gresta et al., 2009). The flowering period of this spice extends over two or three weeks in which the flowers are picked by hands and the dark red stigmas are separated manually. The stigmas from 150,000 to 200,000 flowers are required to produce 1 kg of pure dried saffron (Schmidt et al., 2007).
Crocus sativus L. is comprised mainly of carbohydrates (63%) including starch, reducing sugars, gums, pectin, pentosans, and dextrins (% w/w). Moisture (10%), protein (12%), fat (5%), crude fiber (5%), minerals (5%) and vitamins are other components in this plant (Rios et al., 1996). A variety of biologically active substances have been isolated from saffron. The volatile compounds of saffron consist of more than 34 components that are mainly terpenes, terpene alcohols and their esters. There are three main secondary metabolites including crocin, picrocrocin and safranal in saffron (Liakopoulou-Kyriakides and Kyriakidis, 2002, Pfander and Wittwer, 1975). Additionally, saffron also contains crocetin, which is derived from the hydrolysis of crocin. The chemical structures of these secondary metabolites are presented in Fig. 1.
Recent studies have supported the medicinal properties of saffron as an antidepressant (Ghasemi et al., 2015, Kashani et al., 2016), antioxidant (Hosseinzadeh et al., 2009, Ochiai et al., 2004), cardioprotective (Goyal et al., 2010, Zhang et al., 2009), memory enhancer (Abe and Saito, 2000, Ghadrdoost et al., 2011, Hosseinzadeh and Ziaei, 2006), and neuroprotective (Mehri et al., 2012). Saffron and its constituents have been extensively investigated for its anti-cancer activity and it has been suggested as a potential dietary agent for prevention and treatment of a large number of cancers (Ashrafi et al., 2015, Aung et al., 2007, Li et al., 2015, Samarghandian et al., 2010).
Cancer is characterized by uncontrolled growth of cells and results from complex interactions between inherited genetic and environmental factors (Hemminki and Mutanen, 2001, Pharoah et al., 2004). Cancer is a major public health problem worldwide and a leading cause of death in both economically developed and developing countries. The burden of cancer continues to grow as a result of growth and aging of the population, especially in less developed countries (Torre et al., 2015). It has been estimated that about 1600 Americans per day died from cancer in 2016, where the lung and bronchus, prostate, breast, and colorectal cancers account for 46% of all these cancer deaths (Siegel et al., 2016).
The most common treatments of cancer are surgery, radiation therapy, and chemotherapy (Society, 2013); however, surgical tumor removal is extremely invasive and chemo and radiation therapies are accompanied by various side effects such as pain, fatigue, osteopenia and osteoporosis, cardiotoxicity, cognitive deficits, infertility, pulmonary dysfunction, sexual dysfunction, and emotional distress (Siegel et al., 2012). Therefore, the requirement for novel and less toxic agents that can improve outcomes and have fewer side effects and morbidity is important. Chemoprevention of cancer is a novel way of cancer treatment in which the administrations of one or several natural or synthetic chemical compounds inhibit, reverse or suppress tumor formation (Cazzaniga and Bonanni, 2012, Sporn and Suh, 2000). In recent years, there has been increasing interest in the use of natural compounds as potential chemo-preventive agents with fewer side effects (Lin and Lin-Shiau, 2001, Shafiee et al., 2017, Shankar et al., 2007). Indeed, it has been estimated that about 60% of anticancer/anti-infectious drugs already on the market or under clinical investigations are derived from natural origins (Wang et al., 2007).
Among all natural sources of natural compounds, Crocus sativus L is receiving particular attention due to its potential chemo-preventive properties (Escribano et al., 1996, Kim et al., 2014, Nair et al., 1991). This review summarizes the anticancer properties of saffron and its components in preclinical in vitro and in vivo studies.
Section snippets
Methods
We conducted a non-systematic review of the literature. A search of English-language literature was performed using Scopus, EMBASE and PubMed. We applied no restriction in time. Articles were searched using the keywords “Lung”, “breast”, “skin”, “prostate”, “leukemia”, “cancer”, “neoplasm”, “tumor”, “malignancy”, “saffron”, “crocus sativus”, “crocin”, “crocetin”, “picrocrocin”, and “safranal”. Articles relevant to the subject were included. Additional papers known to the authors were also
Lung cancer
Lung cancer is the leading cause of cancer death among adults in the United States, with more than one-quarter (27%) of cancer deaths in 2016 (Siegel et al., 2016). Lung cancer is categorized into two types; small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), in which the latter can be further divided into adenocarcinoma, squamous cell carcinoma and large cell carcinoma (Brambilla et al., 2001). The effectiveness of lung cancer treatment is very limited and a 5-year survival
Breast cancer
Breast cancer is the most common malignancy of women worldwide which is expected to account for 29% of all newly diagnosed cases of cancer in women in 2016 (Siegel et al., 2016). Compared with lung cancer which is the leading cause of cancer death in women aged 60 years or older, the incidence of breast cancer is higher at younger ages (Siegel et al., 2016). Surgical treatment for breast cancer involves either breast-conserving surgery (BCS) or mastectomy (Miller et al., 2016). Due to
Leukemia
Leukemia is the most commonly diagnosed cancer in children (30%) and the second most prevalent cancer (14%) after brain and central nervous system (CNS) tumors among adolescents (Siegel et al., 2016). It has been reported that since the mid-1970 s, the 5-year relative survival rate of leukemia has increased from 50% to 87% (Howlader et al., 2015).
In a study examining the effects of crocin on human promyelocytic leukemia cells, HL-60 cells, Sun et al. showed that crocin had a potently inhibitory
Skin cancer
Skin cancer is a preventable and commonly diagnosed cancer in the US with more than 2 million cases per year (Patel et al., 2011). Skin cancers are mainly divided into two major groups of melanoma and non-melanoma skin cancers (NMSCs), in which the latter can be further divided to basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) (Razi et al., 2015). It is now clearly understood that excessive ultraviolet (UV) radiation exposure has detrimental effects and is a known cause of skin
Prostate cancer
Prostate cancer is the second most common cause of cancer death (after lung and bronchus) among men in the United States (Siegel et al., 2016). The estimated median age at diagnosis of prostate cancer is 66 years and the majority (64%) of survivors are over the age of 70 years (Miller et al., 2016). The 5-year relative survival rate for all stages increased to 99% in the recent time period (2005–2011) vs. 83% in the late 1980s, an increase of 16% (Miller et al., 2016).
D'Alessandro et al.,
Potential chemopreventive and anticancer mechanisms of saffron and its active constituents
The exact mechanisms underlying cancer chemo-preventive activities of saffron and its components are not yet clearly understood; however, several mechanisms have been suggested to take part (Fig. 2). In the following section, we have discussed these potential mechanisms in details.
Conclusion
There are studies showing that saffron and its major bioactive components including crocin reduce cell proliferation and tumor growth in both cellular and animal studies. Recently, the drug-carrier potential of nanoparticles in cancer therapy attracted attention in the management of cancer complications and provided a new research area for therapy purposes. Stabilized nanoliposomal particles decrease drug cytotoxicity and increase the efficacy of chemotherapy in patients. In line with this,
Funding
The financial support was provided by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran, under Grant 951824.
Conflict of interest
The authors have no conflict of interest to declare.
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2022, Food ChemistryCitation Excerpt :Saffron is composed of various types of ingredients, including terpenoids, flavonoids, phenolic acids, alkaloids, anthraquinones, saponins et al. (Mohtashami et al., 2021). Terpenoids are the main components in saffron, including monoterpenes, diterpenes, triterpenes and tetraterpenes, and among them, crocin, safranal and picrocrocin were reported to be the most bioactive ingredients (Boskabady & Farkhondeh, 2016; Khorasanchi et al., 2018; Roshanravan & Ghaffari, 2022). Particularly, crocins (crocetin esters) have the highest contents and account for 6 % to 16 % of dry weight (Abu-Izneid et al., 2020), and thus they have drawn the most attention in in vitro and in vivo studies.