Strawberry tree honey in combination with 5-fluorouracil enhances chemosensitivity in human colon adenocarcinoma cells Afrin, Sadia Quiles Morales, José Luis Strawberry tree honey 5-fluorouracil Synergistic effect Reactive oxygen species Apoptosis Colon cancer prevention The authors would like to thank Prof. Gavino Sanna, Department of Chemistry and Pharmacy (University of Sassari, Italy), for providing STH samples. Tamara Y. Forbes-Hernandez is supported by a "Juan de la Cierva-Formacion" post-doctoral contract. Colorectal cancer remains a challenging health burden worldwide. This study aimed to assess the potentiality of Strawberry tree honey (STH), a polyphenol-enriched food, to increase the effectiveness of 5-Fluorouracil (5-FU) in adenocarcinoma (HCT-116) and metastatic (LoVo) colon cancer cell lines. The combined treatment reduced cell viability and caused oxidative stress, by increasing oxidative biomarkers and decreasing antioxidant defence, in a more potent way compared to 5-FU alone. The expression of endoplasmic reticulum (ATF-6, XBP-1) and MAPK (p-p38 MAPK, p-ERK1/2) markers were also elevated after the combined treatment, enhancing the cell cycle arrest through the modulation of regulatory genes (i.e., cyclins and CDKs). Apoptotic gene (i.e., caspases) expressions were also increased after the combined treatment, while those of proliferation (i.e., EGFR), cell migration, invasion (i.e., matrix metallopeptidase) and epithelial–mesenchymal transition (N-cadherin, β-catenin) were suppressed. Finally, the combined treatment led cell metabolism towards a quiescent stage, by reducing mitochondrial respiration and glycolysis. In conclusion, this work represents an initial step to highlight the possibility to use STH in combination with 5-FU in the treatment of colon cancer, even if further in vitro an in vivo studies are strongly needed to confirm the possible chemo-sensitizing effects of STH. 2021-11-08T07:30:00Z 2021-11-08T07:30:00Z 2021-08-11 info:eu-repo/semantics/article Sadia Afrin... [et al.]. Strawberry tree honey in combination with 5-fluorouracil enhances chemosensitivity in human colon adenocarcinoma cells, Food and Chemical Toxicology, Volume 156, 2021, 112484, ISSN 0278-6915, [https://doi.org/10.1016/j.fct.2021.112484] http://hdl.handle.net/10481/71337 10.1016/j.fct.2021.112484 eng http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial-SinDerivadas 3.0 España Elsevier