title: Phytochemical profile and apoptotic activity of Onopordum cynarocephalum.
abstract: A phytochemical investigation of acetone and chloroform extracts of the aerial parts of Onopordum cynarocephalum Boiss. et Blanche was carried out. It led to the isolation of two new sesquiterpenes, the elemane aldehyde (2) and the eudesmane (11), together with 15 known compounds: two lignans (1 and 15) and 13 sesquiterpenes (3-10, 12-14, 16, 17). The structures were elucidated by spectroscopic analyses, especially 1D and 2D NMR spectra. The anti-growth effect against three human melanoma cell lines, M14, A375, and A2058, of the different extracts and compounds of O. cynarocephalum was also investigated. Among them, the chloroform extract exhibited the strongest biological activity, while the most active compounds were the lignan arctigenin (1), and the sesquiterpenes, compounds 3, 5, and 6 belonging to the elemane type, and 7 belonging to the eudesmane type. Our data also demonstrate that acetone and chloroform extracts induce, in the A375 cell line, apoptotic cell death that could be related to an overall action of the compounds present, but in particular to the lignans arctigenin (1) and the sesquiterpenes compounds 3-8 and 16. In fact, these molecules were able to induce a high DNA fragmentation, correlated to a significant increase of the caspase-3 enzyme activity. Furthermore, apoptosis appears to be mediated, at least in part, via PTEN activity and the inhibition of Hsp70 expression.
authors.affiliation: Department of Chemistry of Natural Products, University of Naples Federico II, Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Formisano
authors.forename: Daniela
authors.initials: D
authors.lastname: Rigano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Russo
authors.forename: Venera
authors.initials: V
authors.lastname: Cardile
authors.forename: Silvia
authors.initials: S
authors.lastname: Caggia
authors.forename: Nelly
authors.initials: N
authors.lastname: Apostolides Arnold
authors.forename: Angela
authors.initials: A
authors.lastname: Mari
authors.forename: Sonia
authors.initials: S
authors.lastname: Piacente
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosselli
authors.forename: Felice
authors.initials: F
authors.lastname: Senatore
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruno
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D000081222:Monocyclic Sesquiterpenes; D031183:Onopordum / Q000737:chemistry*; D051059:PTEN Phosphohydrolase / Q000187:drug effects / Q000378:metabolism; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045787:Sesquiterpenes, Eudesmane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D018840:HSP70 Heat-Shock Proteins; D017705:Lignans; D000081222:Monocyclic Sesquiterpenes; D010936:Plant Extracts; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; C579703:elemane aldehyde; C015872:eudesmane; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3; C071942:arctigenin