Phenolic compounds from Mediterranean foods as nutraceutical tools for the prevention of cancer: The effect of honey polyphenols on colorectal cancer stem-like cells from spheroids

Abstract Chemoresistance and development of relapses are ascribable to a rare cell population of tumour mass: cancer stem cells (CSCs). Targeting CSCs could increase patients' survival rate and it is important to identify molecules that can act on the main pathways of these cells. Natural bioactive compounds, of which Manuka honey (MH) is rich, could be a good opportunity to target them. This work aims to evaluate the effect of MH on CSCs-like from human colorectal carcinoma (HCT-116 cell line) enriched through the in vitro sphere-forming assay. The results showed that MH reduced the volume of the entire culture of spheroids, affecting also their morphological parameters and induced apoptosis and ROS intracellular accumulation in CSCs-like. In addition, MH decreased the mRNA expression of one of ABC transporters (ABCG2) and affected self-renewal ability through the downregulation of the mRNA expression of one of the receptor membranes of Wnt/β-catenin pathway (Frizzled 7).