Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human
breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human
breast cancer cell growth via a
caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-
galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes,
p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in
cancer cells, modulating
DNA hypomethylation and
lysine acetylation levels in total
proteins. Cell growth arrest correlates with increased
reactive oxygen species (ROS) production in AEs treated
breast cancer cells. Inhibition of ROS generation by
N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits
breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke
polyphenols could be a promising dietary tool either in
cancer chemoprevention or/and in
cancer treatment as a nonconventional, adjuvant
therapy.