title: Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM-p53 cascade in colon cancer cell lines.
abstract: The Mediterranean diet is rich in extra virgin olive oil (EVOO) and associated with a lower incidence of colorectal cancer. EVOO contains phenolic extracts with potential anticarcinogenic activity.
  
  
  OBJECTIVE
  To assess the anticancer properties of EVOO phenolic extracts using in vitro models.
  
  
  METHODS
  Phenolic profiles of two different EVOOs (A and B) were determined. RKO and HCT116 (both p53 proficient), SW480 (p53 mutant) and HCT116(p53-/-) (p53 knocked out) cell lines were treated with EVOO extracts and assessed for cell viability. Apoptosis was determined by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and changes in Bax transcript levels. Cell cycle analysis was determined by flow cytometry and western blots. To confirm the data, analysis of cell viability and cell cycle was performed with purified pinoresinol.
  
  
  RESULTS
  Chemical characterization showed that pinoresinol is the main phenol in EVOO-A, and oleocanthal predominates in EVOO-B. Only EVOO-A affected cell viability, which was significantly more pronounced in p53-proficient cells. At a concentration of 200 nM, p53-proficient cells showed increased apoptosis and G(2)/M arrest. In p53-proficient cells, ataxia telangiectasia mutated (ATM) and its downstream-controlled proteins were upregulated after treatment, with a parallel decrease of cyclin B/cdc2. Identical results on cell viability and cell cycle were obtained with purified pinoresinol, but this required a higher concentration than in EVOO-A.
  
  
  CONCLUSIONS
  Our results demonstrate that pinoresinol-rich EVOO extracts have potent chemopreventive properties and specifically upregulate the ATM-p53 cascade. This result was achieved at substantially lower concentrations in EVOO than with purified pinoresinol, indicating a possible synergic effect between the various polyphenols in olive oil.
authors.affiliation: Department of Internal Medicine, Baylor Research Institute and Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Fini
authors.forename: Erin
authors.initials: E
authors.lastname: Hotchkiss
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fogliano
authors.forename: Giulia
authors.initials: G
authors.lastname: Graziani
authors.forename: Marco
authors.initials: M
authors.lastname: Romano
authors.forename: Edward B
authors.initials: EB
authors.lastname: De Vol
authors.forename: Huanying
authors.initials: H
authors.lastname: Qin
authors.forename: Michael
authors.initials: M
authors.lastname: Selgrad
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
authors.forename: Luigi
authors.initials: L
authors.lastname: Ricciardiello
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D017705:Lignans / Q000494:pharmacology*; D000069463:Olive Oil; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005663:Furans; D017705:Lignans; D000069463:Olive Oil; D010938:Plant Oils; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C103298:pinoresinol