title: Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.
abstract: 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.
authors.affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mileo
authors.affiliation: CNR, Institute of Sciences of Food Production (ISPA), Via Amendola 122/O, 70126 Bari, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Di Venere
authors.affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Abbruzzese
authors.affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Miccadei
mesh_terms: D000111:Acetylcysteine / Q000633:toxicity; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D031943:Cynara scolymus / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D059808:Polyphenols / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D059808:Polyphenols; D017382:Reactive Oxygen Species; D000111:Acetylcysteine