Artichoke polyphenols sensitize human breast cancer cells to chemotherapeutic drugs via a ROS-mediated downregulation of flap endonuclease 1
- Resource Type
- Authors
- Stefania Miccadei; Stefania Mardente; Donato Di Venere; Anna Maria Mileo
- Source
- Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)
Oxidative medicine and cellular longevity (Online) 2020 (2020): 1–11. doi:10.1155/2020/7965435
info:cnr-pdr/source/autori:Mileo, Anna Maria; Di Venere, Donato; Mardente, Stefania; Miccadei, Stefania/titolo:Artichoke Polyphenols Sensitize Human Breast Cancer Cells to Chemotherapeutic Drugs via a ROS-Mediated Downregulation of Flap Endonuclease 1/doi:10.1155%2F2020%2F7965435/rivista:Oxidative medicine and cellular longevity (Online)/anno:2020/pagina_da:1/pagina_a:11/intervallo_pagine:1–11/volume:2020
Oxidative Medicine and Cellular Longevity
- Subject
- Aging
Paclitaxel
Article Subject
Flap Endonucleases
MAP Kinase Signaling System
DNA damage
medicine.medical_treatment
Down-Regulation
Breast Neoplasms
Biochemistry
Gene Expression Regulation, Enzymologic
Nrf2
chemistry.chemical_compound
Downregulation and upregulation
Cynara scolymus
medicine
Humans
FEN1
cynara scolymus
down-regulation
female
flap endonucleases
gene expression regulation, enzymologic
humans
MAP kinase signaling system
MCF-7 cells
paclitaxel
polyphenols
reactive oxygen species
breast neoplasms
chemistry.chemical_classification
Chemotherapy
Reactive oxygen species
QH573-671
Chemistry
Cell growth
breast cancer
Polyphenols
ROS
Cell Biology
General Medicine
artichoke polyphenols
Apoptosis
Cancer cell
MCF-7 Cells
Cancer research
Female
Reactive Oxygen Species
Cytology
Research Article
- Language
- English
Combined treatment of several natural polyphenols and chemotherapeutic agents is more effective comparing to the drug alone in inhibiting cancer cell growth. Polyphenolic artichoke extracts (AEs) have been shown to have anticancer properties by triggering apoptosis or reactive oxygen species- (ROS-) mediated senescence when used at high or low doses, respectively. Our aim was to explore the chemosensitizing potential of AEs in order to enhance the efficacy of conventional chemotherapy in breast cancer cells. We employed breast cancer cell lines to assess the potential synergistic effect of a combined treatment of AEs/paclitaxel (PTX) or AEs/adriamycin (ADR) and to determine the underlying mechanisms correlated to this potential therapeutic approach. Our data shows that AEs/PTX reduced cell proliferation by increasing DNA damage response (DDR) mediated by Flap endonuclease 1 (FEN1) downregulation that results into enhanced breast cancer cell sensitivity to chemotherapeutic drugs. We demonstrated that ROS/Nrf2 and p-ERK pathways are two molecular mechanisms involved in the synergistic effect of AEs plus PTX treatment. To highlight the role of ROS herein, we report that the addition of antioxidant N-acetylcysteine (NAC) significantly decreased the antiproliferative effect of the combined treatment. A combined therapy could be able to reduce the dose of chemotherapeutic drugs, minimizing toxicity and side effects. Our results suggest the use of artichoke polyphenols as ROS-mediated sensitizers of chemotherapy paving the way for innovative and promising natural compound-based therapeutic strategies in oncology.