%L uninimx7844 %D 2023 %V 427 %X Manuka honey, which is rich in pinocembrin, quercetin, naringenin, salicylic, p-coumaric, ferulic, syringic and 3,4-dihydroxybenzoic acids, has been shown to have pleiotropic effects against colon cancer cells. In this study, potential chemosensitizing effects of Manuka honey against 5-Fluorouracil were investigated in colonspheres enriched with cancer stem cells (CSCs), which are responsible for chemoresistance. Results showed that 5-Fluorouracil increased when it was combined with Manuka honey by downregulating the gene expression of both ATP-binding cassette sub-family G member 2, an efflux pump and thymidylate synthase, the main target of 5-Fluorouracil which regulates the ex novo DNA synthesis. Manuka honey was associated with decreased self-renewal ability by CSCs, regulating expression of several genes in Wnt/β-catenin, Hedgehog and Notch pathways. This preliminary study opens new areas of research into the effects of natural compounds in combination with pharmaceuticals and, potentially, increase efficacy or reduce adverse effects. %R doi:10.1016/j.foodchem.2023.136684 %P 136684 %J Food Chemistry %A Danila Cianciosi %A Yasmany Armas Diaz %A José M. Alvarez-Suarez %A Xiumin Chen %A Di Zhang %A Nohora Milena Martínez López %A Mercedes Briones Urbano %A José L. Quiles %A Adolfo Amici %A Maurizio Battino %A Francesca Giampieri %T Can the phenolic compounds of Manuka honey chemosensitize colon cancer stem cells? A deep insight into the effect on chemoresistance and self-renewal