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

Biochem Biophys Res Commun. 2014 Jul 18;450(1):652-8. doi: 10.1016/j.bbrc.2014.06.029. Epub 2014 Jun 14.


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.

Keywords: Cell cycle; Colorectal carcinoma; Epigenetic control; In vitro; Indicaxanthin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Betaxanthins / chemistry
  • Betaxanthins / isolation & purification
  • Betaxanthins / pharmacology*
  • Caco-2 Cells
  • Cell Proliferation / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p16 / agonists*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Humans
  • Opuntia / chemistry*
  • Plant Extracts / pharmacology*
  • Pyridines / chemistry
  • Pyridines / isolation & purification
  • Pyridines / pharmacology*


  • Antineoplastic Agents
  • Betaxanthins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Plant Extracts
  • Pyridines
  • indicaxanthin