title: Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and Activity.
abstract: BACKGROUND
  Recently, we have shown anti-proliferative and pro-apoptotic effects of indicaxanthin associated with epigenetic modulation of the onco-suppressor p16INK4a in the human colon cancer cell line CACO2. In the present study, the epigenetic activity of indicaxanthin and the mechanisms involved were further investigated in other colorectal cancer cell lines.
  
  
  METHODS
  LOVO1, CACO2, HT29, HCT116, and DLD1 cells were used to evaluate the potential influence of consistent dietary concentrations of indicaxanthin on DNA methylation, and the epigenetic mechanisms involved were researched.
  
  
  RESULTS
  Indicaxanthin exhibited anti-proliferative activity in all cell lines but HT29, induced demethylation in the promoters of some methylation-silenced onco-suppressor genes involved in colorectal carcinogenesis (p16INK4a, GATA4, and ESR1), and left unchanged others which were basally hypermethylated (SFRP1 and HPP1). In apparent contrast, cell exposure to indicaxanthin increased DNMT gene expression, although indicaxanthin appeared to be an inhibitor of DNMT activity. Indicaxanthin also increased the expression of genes involved in DNA demethylation. Finally, an in silico molecular modelling approach suggested stable binding of indicaxanthin at the DNMT1 catalytic site.
  
  
  CONCLUSIONS
  Our findings contribute to new knowledge in the field of phytochemicals and specifically suggest dietary indicaxanthin as a potential epigenetic agent to protect colon cells against tumoral alterations.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Universitx00E0; di Palermo, Palermo, Italy.
authors.forename: Flores
authors.initials: F
authors.lastname: Naselli
authors.forename: Nigel Junior
authors.initials: NJ
authors.lastname: Belshaw
authors.forename: Carla
authors.initials: C
authors.lastname: Gentile
authors.forename: Marco
authors.initials: M
authors.lastname: Tutone
authors.forename: Luisa
authors.initials: L
authors.lastname: Tesoriere
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Livrea
authors.forename: Fabio
authors.initials: F
authors.lastname: Caradonna
mesh_terms: D050860:Betaxanthins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic; D006801:Humans; D011725:Pyridines / Q000494:pharmacology*
chemical_list: D050860:Betaxanthins; D011725:Pyridines; C469628:indicaxanthin