title: Mangiferin blocks proliferation and induces apoptosis of breast cancer cells via suppression of the mevalonate pathway and by proteasome inhibition.
abstract: Mangiferin is a natural xanthone glycoside with therapeutic potential. Herein, its cytotoxic properties were explored in a human cell model of breast adenocarcinoma. The results supported the multi-target nature of mangiferin action, as the inhibition of three enzymatic systems, namely HMG-CoA reductase, the proteasome and plasmin, respectively in charge of regulating cholesterol homeostasis, protein turnover and cell adhesion, was documented for the first time. Globally, mangiferin was able to selectively block breast cancer cell growth by inducing apoptosis and by arresting cell proliferation through a combined action on cholesterol and proteasome pathways, as well as to inhibit plasmin-mediated mechanisms of cell migration.
authors.affiliation: University of Camerino, School of Bioscience and Veterinary Medicine, Camerino, Italy. massimiliano.cuccioloni@unicam.it.
authors.forename: M
authors.initials: M
authors.lastname: Cuccioloni
authors.affiliation: University of Camerino, School of Bioscience and Veterinary Medicine, Camerino, Italy. massimiliano.cuccioloni@unicam.it.
authors.forename: L
authors.initials: L
authors.lastname: Bonfili
authors.affiliation: University of Camerino, School of Bioscience and Veterinary Medicine, Camerino, Italy. massimiliano.cuccioloni@unicam.it.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-9835-8446
authors.initials: M
authors.lastname: Mozzicafreddo
authors.affiliation: University of Camerino, School of Bioscience and Veterinary Medicine, Camerino, Italy. massimiliano.cuccioloni@unicam.it.
authors.forename: V
authors.initials: V
authors.lastname: Cecarini
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Scuri
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cocchioni
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Nabissi
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Santoni
authors.affiliation: University of Camerino, School of Bioscience and Veterinary Medicine, Camerino, Italy. massimiliano.cuccioloni@unicam.it.
authors.forename: A M
authors.identifier: http://orcid.org/0000-0003-0461-1346
authors.initials: AM
authors.lastname: Eleuteri
authors.affiliation: University of Camerino, School of Bioscience and Veterinary Medicine, Camerino, Italy. massimiliano.cuccioloni@unicam.it.
authors.forename: M
authors.initials: M
authors.lastname: Angeletti
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D001943:Breast Neoplasms; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005341:Fibrinolysin; D006801:Humans; D008798:Mevalonic Acid / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D044004:Xanthones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D015820:Cadherins; D061988:Proteasome Inhibitors; D044004:Xanthones; C013592:mangiferin; D002784:Cholesterol; D005341:Fibrinolysin; D046988:Proteasome Endopeptidase Complex; D008798:Mevalonic Acid