Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (Caco-2) cells

Fabio Caradonna, Luisa Tesoriere, Flores Naselli, Maria Antonia Livrea, Carla Gentile, Daniele Bellavia, Flores Naselli, Alessandro Attanzio, Luisa Tesoriere, Fabio Caradonna, Maria A. Livrea, Carla Gentile, Alessandro Attanzio, Daniele Bellavia

Risultato della ricerca: Article

28 Citazioni (Scopus)

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 p16INK4a 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. © 2014 Elsevier Inc. All rights reserved.
Lingua originaleEnglish
pagine (da-a)652-658
Numero di pagine7
RivistaBiochemical and Biophysical Research Communications
Volume450
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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