## 1 Introduction  
Saffron (_Crocus sativus_ L.) is a highly profitable crop mainly cultivated in Iran, which accounts for 80-90% of the world's production. Other significant producing countries include India, Morocco, Greece, Spain, Italy, China, and Afghanistan. The production of saffron spice, derived from the dried stigma of the flowers, is an exceptionally labor-intensive process which requires approximately 150,000 to 200,000 flowers to yield just 1 kg, thus resulting in its reputation as the most expensive spice globally [1]. Since only the stigmas are used, there is growing interest in exploring the potential uses of the residues resulting from saffron cultivation. Some researchers have investigated the possible uses of the floral wastes remaining after stigma removal, including the elaboration of novel food products [2] or the extraction of bioactive compounds such as natural antioxidants [3], etc. In contrast, other parts of the saffron plant with low to no commercial value have received considerably less attention. It is estimated that 1500 kg of leaves are involved in the production of each kilogram of dry stigmas [4]. This represents a substantial biomass with greater potential for innovative applications that could boost the overall sustainability and profitability of the crop. More recently, innovative approaches have emerged, such as the use of saffron leaf extracts as a reducing and stabilizing agent in the green synthesis of ZnO nanoparticles [5] and to enhance the corrosion resistance of aluminum [6].  
Among the plant metabolites found in saffron leaves, phenolic compounds have been identified as particularly promising due to their antioxidant properties [7]. In addition, [PERSON] et al. (2016) [4] suggested a correlation between the observed antiproliferative effects of the leaf extracts of saffron on human colon adenocarcinoma cells (Caco-2) and its phenolic compounds; which is consistent with [PERSON] et al. (2011) [8] who demonstrated the chemoprotective effect of dietary polyphenols such as quercetin, rutin, myricetin, chrysin, catechins, resveratrol, or xanthohumol in colorectal cancer cell lines. This protective role, considering the potential direct exposure of the intestinal tract to novel products containing saffron extracts, underscores the necessity of exploring natural alternatives for the treatment of one of the most prevalent cancers worldwide: colorectal cancer. Furthermore, there is a significant association between iron and copper intake and colorectal cancer, mainly attributed to the generation of free radicals through Fenton's reaction. In line with this, [PERSON] et al. (2014) [9] demonstrated that chelating the intracellular copper that accumulates in colon cancer cells induces their death without affecting normal cells. Given the exploration of chelators as novel antitumor agents, the expected metal-chelating capacities of phenols from saffron leaves may also offer a promising strategy to slow down the progression of the cancer.  
This research seeks to verify whether the phenolic compounds present in saffron leaves are responsible for the antiproliferative effects previously observed on Caco-2 cells, as suggested by [PERSON] et al. (2016) [4]. This study involved the development of a novel methodology for isolating a phenol-rich fraction, the identification and quantification of its main components using HPLC-DAD/ESI-MS and its evaluation through cell inhibition assays. In addition, the metal-chelating capabilities of the extract on iron and copper ions were also assessed.