TY - JOUR
T1 - Strawberry tree honey in combination with 5-fluorouracil enhances chemosensitivity in human colon adenocarcinoma cells
AU - Afrin, Sadia
AU - Giampieri, Francesca
AU - Cianciosi, Danila
AU - Alvarez-Suarez, José M.
AU - Bullon, Beatriz
AU - Amici, Adolfo
AU - Quiles, Josè L.
AU - Forbes-Hernández, Tamara Y.
AU - Battino, Maurizio
N1 - Publisher Copyright:
© The Authors
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - 5-Fluorouracil
KW - Apoptosis
KW - Colon cancer prevention
KW - Reactive oxygen species
KW - Strawberry tree honey
KW - Synergistic effect
UR - http://www.scopus.com/inward/record.url?scp=85112367285&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2021.112484
DO - 10.1016/j.fct.2021.112484
M3 - Artículo
C2 - 34389368
AN - SCOPUS:85112367285
SN - 0278-6915
VL - 156
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
M1 - 112484
ER -
