Honey has always been used not only as a food/sweetener but also as a medicine since ancient times. The quality and composition depend on many factors, including the botanical origin, the environmental, processing and storage conditions[1]. The nutritional characteristics and the preventive/therapeutic effect of honey are due to its composition: it contains over 180 different types of compounds including water, carbohydrates, enzymes, amino acids, minerals, vitamins and different phytochemicals[2] . Among the different effects on health, those most studied in the scientific literature are its antibacterial activity[3] and the antioxidant capacity[4]. In recent years the potential anticancer effect of honey, in several tumor cell lines, has also been a reason of study[5]. Among different types of honey, Manuka, has shown a high anticancer effect, especially in colon cancer cells (LoVo and HCT-116)[6,7] while it is little known on its effect in cancer stem cells' (CSCs; a rare population of cells within the tumor mass that seem to be responsible for the tumor onset) chemoresistance and the presence of relapse [8]. Therefore, the effect of Manuka honey on CSCs-like was evaluated. In general, CSCs-like were enriched from the monolayer population of HCT-116 through the in vitro sphere forming assay[9]. This honey was able to modify the morphological parameters of the spheroids, reducing the size and volume of the entire culture. The treatment of CSCs-like enriched colonospheres with Manuka honey also led to an intracellular accumulation of ROS and induction of apoptosis. Furthermore, through real-time PCR, down-regulation of ABCG2 gene expression (one of the efflux pumps closely associated with the chemoresistance phenotype) was observed.
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