title: Feijoa sellowiana derived natural Flavone exerts anti-cancer action displaying HDAC inhibitory activities.
abstract: Curative properties of some medicinal plants such as the Feijoa sellowiana Bert. (Myrtaceae), have been often claimed, although the corresponding molecular mechanism(s) remain elusive. We report here that the Feijoa acetonic extract exerts anti-cancer activities on solid and hematological cancer cells. Feijoa extract did not show toxic effects on normal myeloid progenitors thus displaying a tumor-selective activity. In the Feijoa acetonic extract, fractionation and subsequent purification and analyses identified Flavone as the active component. Flavone induces apoptosis which is accompanied by caspase activation and p16, p21 and TRAIL over-expression in human myeloid leukemia cells. Use of ex vivo myeloid leukemia patients blasts confirms that both the full acetonic Feijoa extract and its derived Flavone are able to induce apoptosis. In both cell lines and myeloid leukemia patients blasts the apoptotic activity of Feijoa extract and Flavone is accompanied by increase of histone and non-histone acetylation levels and by HDAC inhibition. Our findings show for the first time that the Feijoa apoptotic active principle is the Flavone and that this activity correlates with the induction of HDAC inhibition, supporting the hypothesis of its epigenetic pro-apoptotic regulation in cancer systems.
authors.affiliation: Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, vico L. De Crecchio 7, 80138 Napoli, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bontempo
authors.forename: Luigi
authors.initials: L
authors.lastname: Mita
authors.forename: Marco
authors.initials: M
authors.lastname: Miceli
authors.forename: Antonella
authors.initials: A
authors.lastname: Doto
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.forename: Floriana
authors.initials: F
authors.lastname: De Bellis
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Conte
authors.forename: Annunziata
authors.initials: A
authors.lastname: Minichiello
authors.forename: Fabio
authors.initials: F
authors.lastname: Manzo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carafa
authors.forename: Adriana
authors.initials: A
authors.lastname: Basile
authors.forename: Daniela
authors.initials: D
authors.lastname: Rigano
authors.forename: Sergio
authors.initials: S
authors.lastname: Sorbo
authors.forename: Rosa
authors.initials: R
authors.lastname: Castaldo Cobianchi
authors.forename: Ettore Mariano
authors.initials: EM
authors.lastname: Schiavone
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Mariacarla
authors.initials: M
authors.lastname: De Simone
authors.forename: MariaTeresa
authors.initials: M
authors.lastname: Vietri
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sica
authors.forename: Francesco
authors.initials: F
authors.lastname: Bresciani
authors.forename: Angel R
authors.initials: AR
authors.lastname: de Lera
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Molinari
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D031646:Feijoa / Q000737:chemistry*; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D056572:Histone Deacetylase Inhibitors; D010936:Plant Extracts; C043562:flavone