title: Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16(INK4a) gene in human colorectal carcinoma (Caco-2) cells.
abstract: Phytochemicals may exert chemo-preventive effects on cells of the gastro-intestinal tract by modulating epigenome-regulated gene expression. The effect of the aqueous extract from the edible fruit of Opuntia ficus-indica (OFI extract), and of its betalain pigment indicaxanthin (Ind), on proliferation of human colon cancer Caco-2 cells has been investigated. Whole extract and Ind caused a dose-dependent apoptosis of proliferating cells at nutritionally relevant amounts, with IC50 400±25 mg fresh pulp equivalents/mL, and 115±15 μM (n=9), respectively, without toxicity for post-confluent differentiated cells. Ind accounted for ∼80% of the effect of the whole extract. Ind did not cause oxidative stress in proliferating Caco-2 cells. Epigenomic activity of Ind was evident as de-methylation of the tumor suppressor p16(INK4a) gene promoter, reactivation of the silenced mRNA expression and accumulation of p16(INK4a), a major controller of cell cycle. As a consequence, decrease of hyper-phosphorylated, in favor of the hypo-phosphorylated retinoblastoma was observed, with unaltered level of the cycline-dependent kinase CDK4. Cell cycle showed arrest in the G2/M-phase. Dietary cactus pear fruit and Ind may have chemo-preventive potential in intestinal cells.
authors.affiliation: Dipartimento STEBICEF, Università di Palermo, Palermo, Italy.
authors.forename: Flores
authors.initials: F
authors.lastname: Naselli
authors.affiliation: Dipartimento STEBICEF, Università di Palermo, Palermo, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Tesoriere
authors.affiliation: Dipartimento STEBICEF, Università di Palermo, Palermo, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Caradonna
authors.affiliation: Dipartimento STEBICEF, Università di Palermo, Palermo, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bellavia
authors.affiliation: Dipartimento STEBICEF, Università di Palermo, Palermo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Attanzio
authors.affiliation: Dipartimento STEBICEF, Università di Palermo, Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Gentile
authors.affiliation: Dipartimento STEBICEF, Università di Palermo, Palermo, Italy. Electronic address: maria.livrea@unipa.it.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Livrea
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D050860:Betaxanthins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000819:agonists* / Q000378:metabolism*; D006801:Humans; D029747:Opuntia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D050860:Betaxanthins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D010936:Plant Extracts; D011725:Pyridines; C469628:indicaxanthin
keywords: Cell cycle; Colorectal carcinoma; Epigenetic control; In vitro; Indicaxanthin