Can the phenolic compounds of Manuka honey chemosensitize colon cancer stem cells? A deep insight into the effect on chemoresistance and self-renewal

ABSTR A C T 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-Fluo-rouracil 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/& beta;-catenin, Hedgehog and Notch path-ways. 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.

Automated summary

This study investigated the chemosensitizing effects of Manuka honey against 5-Fluorouracil in colonspheres enriched with cancer stem cells (CSCs). The results showed that combining Manuka honey with 5-Fluorouracil decreased the gene expression of ABC sub-family G member 2 and thymidylate synthase, which are associated with drug resistance and DNA synthesis respectively. Manuka honey also regulated the Wnt/β-catenin, Hedgehog and Notch pathways, reducing the self-renewal ability of CSCs. This preliminary study opens new possibilities for the combination of natural compounds and pharmaceuticals to enhance efficacy or reduce adverse effects.