Manuka honey in combination with 5-Fluorouracil decreases physical parameters of colonspheres enriched with cancer stem-like cells and reduces their resistance to apoptosis

Danila Cianciosi; Tamara Y Forbes-Hernández; Lucia Regolo; José M Alvarez-Suarez; Denise Quinzi; Azzurra Sargenti; Weibin Bai; Lingmin Tian; Francesca Giampieri; Maurizio Battino

doi:10.1016/j.foodchem.2021.131753

Manuka honey in combination with 5-Fluorouracil decreases physical parameters of colonspheres enriched with cancer stem-like cells and reduces their resistance to apoptosis

Food Chem. 2022 Apr 16:374:131753. doi: 10.1016/j.foodchem.2021.131753. Epub 2021 Dec 3.

Affiliations

¹ Department of Clinical Sciences, Polytechnic University of Marche, Ancona 60131, Italy.
² Department of Analytical and Food Chemistry, CITACA, CACTI, University of Vigo - Vigo, Spain.
³ Departamento de Ingeniería en Alimentos. Colegio de Ciencias e Ingenierías. Universidad San Francisco de Quito, Quito, Ecuador 170157, Ecuador; Instituto de Investigaciones en Biomedicina iBioMed, Universidad San Francisco de Quito, Quito, 170157, Ecuador; King Fahd Medical Research Center, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
⁴ CellDynamics isrl, Via Piero Gobetti, 101, 40129, Bologna, Italy.
⁵ Department of Food Science and Engineering, Institute of Food Safety and Nutrition, Guangdong Engineering Technology Center of Food Safety Molecular Rapid Detection, Jinan University, Guangzhou, PR China.
⁶ Department of Clinical Sciences, Polytechnic University of Marche, Ancona 60131, Italy; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander 39011, Spain. Electronic address: f.giampieri@univpm.it.
⁷ Department of Clinical Sciences, Polytechnic University of Marche, Ancona 60131, Italy; Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander 39011, Spain; International Joint Research Laboratory of Intelligent Agriculture and Agri-products Processing, Jiangsu University, Zhenjiang, China. Electronic address: m.a.battino@univpm.it.

PMID: 34883427
DOI: 10.1016/j.foodchem.2021.131753

Abstract

The aim of the present work was to evaluate the in vitro effect of Manuka honey and its combination with 5-Fu, the most common drug used in the treatment of colon cancer, on the morphological and physical parameters of colonspheres enriched with cancer stem-like cells deriving from HCT-116 colon adenocarcinoma cell line and on the apoptosis rate. Manuka honey, alone and more in combination with 5-Fu, reduced the weight, the diameter and mass density of the spheroids and induced apoptosis through the downregulation of many apoptosis inhibitors, including IAPs (Livin, Survivin, XIAP), IGFs (IGF-I, IGF-II and IGF-IR) and HSPs (HSP-27, HSP-60 and HSP-70). These results led to a reduction in the survival ability of cancer stem-like cells, as well as to a chemosensitizing effect of honey towards 5-Fu, considering that apoptosis resistance is one of the main causes of cancer stem-like cells chemoresistance.

Keywords: Apoptosis; Cancer; Chemosensibility; Honey; Spheroids; Stemness.

MeSH terms

Apoptosis
Cell Line, Tumor
Cell Proliferation
Colonic Neoplasms*
Fluorouracil
Honey*
Humans

Substances

Fluorouracil