Carcinogenesis Advance Access originally published online on November 13, 2007
Carcinogenesis 2008 29(1):139-146; 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 75246, USA
2 Department of Internal Medicine, Catholic University, Rome 00168, Italy
3 Department of Nutrition Sciences, University of Naples, Naples 80138, Italy
4 Division of Gastroenterology, Second University of Naples, Naples 80138, Italy
5 Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, TX 75206, USA
* To whom correspondence should be addressed. Tel: +1 214 820 2751; Fax: +1 214 818 9292; Email: luigir{at}baylorhealth.edu
Correspondence may also be addressed to C.Richard Boland. Tel: +1 214 820 2692; Fax: +1 214 818 9292; Email: rickbo{at}baylorhealth.edu
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. 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 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 G2/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. 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.
Abbreviations: ATM, ataxia telangiectasia mutated; CRC, colorectal cancer; EVOO, extra virgin olive oil; MTT, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PCR, polymerase chain reaction
Received June 15, 2007; revised October 31, 2007; accepted November 4, 2007.
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