Carcinogenesis Advance Access published online on November 13, 2007
Carcinogenesis, doi:10.1093/carcin/bgm255
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Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM-p53 cascade in colon cancer cell lines
1 Department of Internal Medicine, Baylor Research Institute, and Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
2 Department of Internal Medicine, Catholic University, Rome, Italy
3 Department of Nutrition Sciences, University of Naples, Naples, Italy
4 Division of Gastroenterology, Second University of Naples, Naples, Italy
5 Institute for Health Care Research and Improvement Baylor Health Care System, Dallas, TX, USA
Address for Correspondence: Dr. Luigi Ricciardiello or Dr. C. Richard Boland, GI Cancer Research Laboratory, Baylor University Medical Center, 3500 Gaston Avenue (250 Hoblitzelle), Dallas, TX, 75246, Phone:+1-214-820-2751 E-mail: luigir{at}baylorhealth.edu ; rickbo{at}baylorhealth.edu
The Mediterranean diet is rich in extra virgin olive oil (EVOO), and associated with a lower incidence of colorectal cancer (CRC). EVOO contains phenolic extracts with potential anti-carcinogenic activity.
Aim: 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 HCT116p53-/- (p53 knocked out) cell lines were treated with EVOO extracts, and assessed for cell viability. Apoptosis was determined by 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 G2/M arrest. In p53-proficient cells, 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.
Conclusion: 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.
Key Words: Colorectal cancer • p53 • ATM • chemoprevention • olive oil
Received June 15, 2007; revised October 31, 2007; accepted November 4, 2007.