Feijoa sellowiana derived natural Flavone exerts anti-cancer action displaying HDAC inhibitory activities.
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.
Bontempo
Paola
P
Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, vico L. De Crecchio 7, 80138 Napoli, Italy.
Mita
Luigi
L
Miceli
Marco
M
Doto
Antonella
A
Nebbioso
Angela
A
De Bellis
Floriana
F
Conte
Mariarosaria
M
Minichiello
Annunziata
A
Manzo
Fabio
F
Carafa
Vincenzo
V
Basile
Adriana
A
Rigano
Daniela
D
Sorbo
Sergio
S
Castaldo Cobianchi
Rosa
R
Schiavone
Ettore Mariano
EM
Ferrara
Felicetto
F
De Simone
Mariacarla
M
Vietri
MariaTeresa
M
Cioffi
Michele
M
Sica
Vincenzo
V
Bresciani
Francesco
F
de Lera
Angel R
AR
Altucci
Lucia
L
Molinari
Anna Maria
AM
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
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D056572:Histone Deacetylase Inhibitors; D010936:Plant Extracts; C043562:flavone